What changed in this filing

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Item 1. Business

2023-03-01 compared with 2022-03-11 · 106 added, 99 removed, 625 unchanged (25% of the section changed)

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Since December 2018, we have sold our patented Primatene MIST ® using a new hydrofluoroalkanes, or HFA, formulation as our sole over-the-counter product.

We are currently developing a portfolio of generic abbreviated new drug applications, or ANDAs, biosimilar insulin product candidates and proprietary product candidates, which are in various stages of development and target a variety of indications.

Five ANDAs and one NDA are currently on file with the FDA.

Additionally, we have one product with tentative FDA approval, Vasopressin, which we plan to launch in the third quarter of 2022, subject to a confidential settlement agreement with the product’s innovator.

Our largest products by net revenues currently include Primatene MIST ® , epinephrine, glucagon, phytonadione, lidocaine, and enoxaparin sodium.

In April 2022, the FDA approved our ganirelix acetate injection 250mg/0.5mL prefilled syringe, which we launched in June 2022.

In July 2022, the FDA approved our vasopressin injection, USP 20 Units/mL, 1 mL single-dose vial, which we launched in August 2022.

In May 2022, the FDA approved our regadenoson injection, 0.08mg/mL, 5mL, single-dose prefilled syringe.

The timing of the launch of this product is subject to a confidential settlement agreement with the product’s innovator.

For the years ended December 31, 2022, 2021, and 2020, we recorded net revenues of $499.0 million, $437.8 million, and $349.8 million, respectively.

We recorded net income of $91.4 million, $62.1 million, and $1.4 million for the years ended December 31, 2022, 2021, and 2020, respectively.

Our largest products by net revenues currently include Primatene Mist ® , glucagon, epinephrine, enoxaparin sodium injection, lidocaine jelly, naloxone, and phytonadione.

In December 2020, the FDA approved our glucagon for injection emergency kit, 1mg, which we launched in February 2021.

Three of the ANDAs and one new drug application, or NDA, are currently on file with the FDA.

Our multiple technological capabilities enable the development of technically challenging products with limited competition.

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To complement our internal growth and expertise, we have made several strategic acquisitions of companies, products and technologies.

These acquisitions collectively have strengthened our core injectable and inhalation product technology infrastructure by providing additional manufacturing, marketing, and research and development capabilities, including manufacturing raw materials, APIs, and other components for our products.

COVID-19 Pandemic

We are actively monitoring the COVID-19 pandemic, including the Omicron variant, and its impact globally.

Currently, our production facilities in all of our locations continue to operate as they had before the COVID-19 pandemic with few changes, other than for enhanced safety measures intended to prevent the spread of the virus.

As a result of the COVID-19 pandemic, during the first half of 2020, sales of Primatene Mist ® and certain hospital products increased, while sales of certain products frequently used in elective procedures, such as Cortrosyn ® and lidocaine products decreased.

We saw these trends continue in late 2020 and early 2021 when COVID cases trended higher.

The sales of these products, frequently used in elective procedures, returned to their normal level by the second quarter of 2021.

Some of our ongoing clinical trials experienced short-term interruptions in the recruitment of patients due to the COVID-19 pandemic, as hospitals prioritize their resources towards the COVID-19 pandemic and governments impose travel restrictions.

Some clinical trials experienced increased expenses due to new protocols to protect participants from COVID-19.

Additionally, certain suppliers had difficulties meeting their delivery commitments.

It is not possible at this time to estimate the complete impact that COVID-19 could have on our business, including our customers and suppliers, as the effects will depend on future developments, which are highly uncertain and cannot be predicted.

Infections may resurge or become more widespread, including due to new variants, and the limitation on our ability to travel and timely sell and distribute our products, as well as any closures or supply disruptions, may be prolonged for extended periods, all of which would have a negative impact on our business, financial condition, and operating results.

Even after the COVID-19 pandemic has subsided, we may continue to experience an adverse impact on our business due to the continued global economic impact of the COVID-19 pandemic.

We cannot anticipate all of the ways in which health epidemics such as COVID-19 could adversely impact our business.

See Item 1A, “Risk Factors” for further discussion of the possible impact of the COVID-19 pandemic on our business.

These acquisitions collectively have strengthened our core injectable and inhalation product technology infrastructure by providing additional manufacturing, marketing, and research and development capabilities, including the ability to manufacture raw materials, API, and other components for our products.

In 2021, we completed the restructuring of our Chinese subsidiary, ANP, resulting in the reduction of ANP’s ownership of Hanxin Pharmaceutical Technology Co., Ltd, or Hanxin to 14%.

See Note 3 in the accompanying “Notes to Consolidated Financial Statements” in this Annual Report on Form 10-K.

As a result of the restructuring, we determined that we have significant influence over Hanxin and as such the retained non-controlling investment in Hanxin is accounted for as an equity method investment.

Hanxin continues to be a related party subsequent to the restructuring.

We primarily target products with high technical barriers to market entry, with a particular focus on the injectable and inhalation markets.

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We are a vertically integrated company with the demonstrated ability to advance a product candidate from the research and development stage through commercialization.

Our capabilities include strong research and development expertise, sophisticated pharmaceutical engineering

capabilities, comprehensive manufacturing capabilities (including the ability to synthesize and manufacture API), a strict quality assurance system, extensive regulatory and clinical experience, and established marketing and distribution relationships.

Our capabilities include strong research and development expertise, sophisticated pharmaceutical engineering capabilities, comprehensive manufacturing capabilities (including the ability to synthesize and manufacture API), a strict quality assurance system, extensive regulatory and clinical experience, and established marketing and distribution relationships.

We believe our vertical integration allows us to achieve better operating efficiencies, accelerated product development, and internal control over product quality.

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● Diversify our revenues by commercializing our product candidates.

Assuming we are successful in developing and obtaining regulatory approvals, we plan to commercialize our product candidates and diversify our revenue sources.

Assuming we successfully develop and obtain regulatory approvals, we plan to commercialize our product candidates and diversify our revenue sources.

We have over 20 product candidates in various stages of development, including generic ANDAs or NDAs, biosimilar product candidates, and proprietary product candidates.

We also expect to expand our internal sales and marketing capabilities and, in some cases, enter into strategic alliances with other pharmaceutical companies to drive market penetration for our product candidates.

● Focus on high-margin generic product opportunities.

We believe that we have significant opportunities for growth driven by our technical expertise in the development of generic product candidates with high technical barriers to market entry.

We believe that we have significant opportunities for growth driven by our technical expertise in developing generic product candidates with high technical barriers to market entry.

We believe that if these product candidates are commercialized, they are likely to face less competition than less technically challenging generic products, which may enable us to earn higher margins for a longer period of time.

We believe that generic competition for these products is likely to be limited because of challenges in product development, manufacturing, or sourcing of raw materials or APIs.

We believe that generic competition for these products will likely be limited because of challenges in product development, manufacturing, or sourcing raw materials or APIs.

● Develop proprietary products.

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or Armstrong, (3) Nanjing Puyan Pharmaceutical Technology Co., Ltd.

(which we renamed Amphastar Nanjing Pharmaceuticals Co., Ltd.), or ANP, (4) Merck’s API Manufacturing Business in Éragny-sur-Epte,

France, in connection with which, we established our French subsidiary, Amphastar France Pharmaceuticals, S.A.S., or AFP, and (5) International Medication Systems (UK) Limited, or IMS UK.

(which we renamed Amphastar Nanjing Pharmaceuticals Co., Ltd.), or ANP, (4) Merck’s API Manufacturing Business in Éragny-sur-Epte, France, in connection with which, we established our French subsidiary, Amphastar France Pharmaceuticals, S.A.S., or AFP, and (5) International Medication Systems (UK) Limited, or IMS UK.

Products we have acquired include Cortrosyn ® and Epinephrine Mist, as well as trade names such as Primatene ® .

We believe that our scientific and managerial expertise and our integration experience have improved the quality of the product lines and companies that we have acquired, which has had, and we believe will continue to have, a positive effect on our results of operations.

For example, in 2018, we received approval from the FDA for the manufacture of semi-purified heparin at our Chinese subsidiary, ANP.

For example, in 2018, we

received approval from the FDA to manufacture semi-purified heparin at our Chinese subsidiary, ANP.

We plan to have ANP manufacture API for certain other products and product candidates.

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● Injectable.

Our injectable product technologies enable us to develop and manufacture generic and proprietary injectables in liquid, lyophilized, suspension, and emulsion forms, as well as the use of pre-filled syringes to facilitate the safety and conveniences to users.

We have multiple injectable manufacturing facilities that include aseptic filling lines dedicated to the sterile production of injectable products.

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● Inhalation and Intranasal.

We are focused on developing a broad range of generic and proprietary inhalation and intranasal products utilizing a variety of delivery technologies.

We are focused on developing a broad range of generic and proprietary inhalation and intranasal products utilizing various delivery technologies.

We have expertise in formulating HFA-based MDIs and DPIs, as well as packaging our inhalation drugs in blister packs and other forms which can be used for loading our products into a variety of inhalation devices.

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● Characterization of complex molecules.

Characterization of complex molecules includes a determination of physicochemical properties, biological activity, immunochemical properties, and purity.

Such characterization is important in the development of a generic product that is considered the same as a reference drug product, which in turn allows the generic drug developer to demonstrate such “sameness” to the FDA, which ultimately allows for interchangeability with the reference drug product.

Complex molecule characterization includes determining physicochemical properties, biological activity, immunochemical properties, and purity.

Such characterization is important in developing a generic product that is considered the same as a reference drug product, which in turn allows the generic drug developer to demonstrate such “sameness” to the FDA, which ultimately allows for interchangeability with the reference drug product.

Complex drugs typically have large molecules composed of a mixture of molecules that differ very slightly from one another.

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As a result, the FDA has signaled that they may require immunogenicity studies as part of the new pathway for biosimilars and biogenerics.

In the past, the FDA has required these studies in connection with the approval of products with complex molecules.

In the past, the FDA has required these studies to approve products with complex molecules.

We have gained expertise in immunogenicity by performing immunogenicity studies in connection with the FDA approval process for our enoxaparin product.

We believe that our experience in conducting these complex immunogenicity studies will be of primary importance in our future efforts to develop complex molecules, biosimilar, and biogeneric product candidates.

We believe that our experience conducting these complex immunogenicity studies will be of primary importance in our future efforts to develop complex molecules, biosimilar, and biogeneric product candidates.

● Peptide and protein product development and production.

The development of peptide and protein drug products utilizes our characterization technology and immunogenicity studies, synthetic capabilities, as well as recombinant DNA, or rDNA, API manufacturing technology.

The development of peptide and protein drug products utilizes our characterization technology and immunogenicity studies, synthetic capabilities, recombinant DNA, or rDNA, and API manufacturing technology.

We have experience using rDNA manufacturing technology, including the genetic engineering of host cells, fermentation to promote cell culture growth, and isolation and purification of the desired protein from the cell culture.

Testing is required to ensure that only the desired protein is included in the finished product through each step.

believe that this technology will allow us to develop protein and peptide drug products.

In December 2020, we received the first-ever FDA approval of a generic version of Glucagon for Injection Emergency Kit.

We believe that this technology will allow us to develop protein and peptide drug products.

In December 2020, we received the first-ever FDA approval for a generic version of Glucagon for Injection Emergency Kit.

The FDA determined our approved peptide product to be bioequivalent and therapeutically equivalent to the reference listed drug, which has rDNA origin.

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Particle engineering is important in the field of pulmonary drug delivery as there is a direct relationship between the properties of a particle and its absorption by the lungs.

We believe our expertise and technology, which applies to particle engineering and physical chemistry, allows us to engineer the size, shape, surface smoothness, and distribution of particles to develop inhalation products that are more easily dispersed through targeted areas.

We believe this expertise will allow us to formulate difficult to disperse inhalation products as well as demonstrate to the FDA the sameness to the reference listed drugs.

We believe our expertise and technology, which applies to particle engineering and physical chemistry, allow us to engineer particles’ size, shape, surface smoothness and distribution to develop inhalation products that are more easily dispersed through targeted areas.

We believe this expertise will allow us to formulate difficult- to-disperse inhalation products and demonstrate the sameness of the reference-listed drugs to the FDA.

● Sustained-release.

We have developed technology to improve drug delivery through sustained-release injectable products.

The purpose of our sustained-release technology is to create products that require less dosing frequency, which we believe can lead to the diminishing of fluctuations of drug concentrations in a patient’s bloodstream that would otherwise require more frequent dosing.

Our sustained-release technology aims to create products that require less dosing frequency, which we believe can lead to diminishing fluctuations of drug concentrations in a patient’s bloodstream that would otherwise require more frequent dosing.

We plan to use our sustained-release technology to develop both generic and proprietary products.

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We have the capability to develop novel formulations to enhance drug delivery.

For certain intranasal medications, novel formulation might be required to increase the drug’s absorption rate to be able to deliver the medication in a safe and efficacious manner.

For certain intranasal medications, novel formulations might be required to increase the drug’s absorption rate to deliver the medication safely and efficiently.

We plan to use our novel formulation with our intranasal epinephrine product.

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● Phytonadione injection, an injection of Vitamin K1 that is used for newborn babies;

● Our portfolio of emergency syringe products, including critical care drugs such as atropine, calcium chloride, dextrose, epinephrine, lidocaine, and sodium bicarbonate, that are provided in pre-filled syringes and are designed for emergency use in hospital settings;

● Our portfolio of emergency syringe products, including critical care drugs such as atropine, calcium chloride, dextrose, epinephrine, lidocaine, and sodium bicarbonate, are provided in pre-filled syringes and are designed for emergency use in hospital settings;

● Morphine injection in prefilled syringe, pain management product indicated for use with Patient Controlled Analgesia (PCA) pumps;

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● Isoproterenol hydrochloride injection, indicated for multiple uses, including mild or transient episodes of heart block that do not require electric shock or pacemaker therapy;

● Ganirelix Acetate Injection, indicated for the inhibition of premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation;

● Vasopressin is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines.

Our Product Candidates

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The development, regulatory approval for and commercialization of our product candidates are subject to numerous risks.

See “Risk Factors” for additional information.

See Item 1A, “Risk Factors” for additional information.

Generic Product Candidates

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We have worked with the FDA to resolve these issues, most recently in 2020 with a Face-to-Face Meeting in which a clear pathway for addressing these issues was created.

We intend to continue to work with the FDA to address their concerns described in the CRL and have received an extension on our response to the CRL.

In September 2022, we responded to the CRL.

We intend to continue to work with the FDA to address their concerns described in the CRL.

However, there can be no guarantee that our response to the CRL will result in timely approval of intranasal naloxone or approval at all.

Intranasal epinephrine

Intranasal epinephrine, a prescription epinephrine nasal spray product candidate, is intended to be used for emergency treatment of allergic reactions, including anaphylaxis to stinging insects, allergen immunotherapy, foods, drugs and other allergens.

Other Proprietary Product Candidates

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In May 2021, we amended the Supply Agreement with MannKind whereby MannKind’s aggregate total commitment of RHI API under the Supply Agreement was modified and extended for an additional year through 2027, which timeframe would have previously lapsed after calendar year 2026.

MannKind has agreed to pay us an amendment fee of $2.0 million.

MannKind agreed to pay us an amendment fee of $2.0 million.

We received the first payment of the amendment fee of $1.0 million in June 2021, which we recognized in net revenues during the year ended December 31, 2021.

The remaining $1.0 million of the amendment fee was received in January 2022 and relates to the amendments to the 2022 supply level and will be recognized ratably to net revenues in 2022.

The remaining $1.0 million of the amendment fee was received in January 2022, which we recognized in net revenues during the year ended December 31, 2022, and relates to the amendments to the 2022 supply level and will be recognized ratably to net revenues in 2022.

For the years ended December 31, 2022, 2021 and 2020, sales of RHI API to MannKind totaled $5.0 million, $6.2 million and $4.9 million, which fulfilled the 2022, 2021 and 2020 commitment of RHI API under the amended Supply Agreement, respectively.

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A significant portion of our customer shipments in any fiscal year relates to orders received and shipped in that fiscal year, generally resulting in a low product backlog relative to total shipments at any time.

We had no significant backlog as of December 31, 2021 and 2020.

However, as of December 31,

2022, we experienced a backlog of approximately $7.0 million for various products, partially as a result of competitor shortages, supplier constraints and labor shortages at our facility in California.

We are currently working on resolving backlog related issues and believe that we will be able to reduce the backlog in the near future.

Historically, our backlog has not been a meaningful indicator of our ability to achieve any particular level of overall revenue or financial performance.

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and Nanjing, China.

We own or lease a total of 56 buildings at six locations in the United States, France and China, that comprise 1.7 million square feet of manufacturing, research and development, distribution,

packaging, laboratory, office and warehouse space.

We own or lease a total of 56 buildings at six locations in the United States, France and China, that comprise 1.8 million square feet of manufacturing, research and development, distribution, packaging, laboratory, office and warehouse space.

Our facilities are regularly inspected by the FDA in connection with our product approvals, and we believe that all of our facilities are being operated in material compliance with the FDA’s cGMP regulations.

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A USDA veterinary permit is required for importation of materials derived from animals or exposed to animal-source materials.

Some of our raw materials sourced from foreign sources are subject to import regulations and permit requirements, including from the USDA.

raw materials sourced from foreign sources are subject to import regulations and permit requirements, including from the USDA.

Recently, USDA enhanced its African swine fever, or ASF, surveillance efforts, including placing restrictions on the importation of pork products from affected countries, such as China, where the first cases of ASF were reported in August 2018.

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If we are unable to import raw materials, rely upon existing supplies of raw materials or manufacture raw materials in sufficient amounts for our manufacturing needs, we may be required to find alternative suppliers or sources of such materials, which would require prior FDA approval for such alternative suppliers or sources of such materials, which would disrupt or delay the manufacturing of our products.

We plan to have ANP manufacture APIs and starting materials for APIs for certain other products and product candidates, including isoproterenol and hyaluronidase, which ANP currently manufactures for Amphastar.

Similarly, on December 27, 2020, the American Innovation in Manufacturing Act of 2020, or AIM Act, was enacted.

The AIM Act directs the United States Environmental Protection Agency to address usage of hydrofluorocarbons, or HFC, by reducing production and consumption of certain HFCs.

One of our products, Primatene MIST ® , utilizes HFCs subject to the AIM Act’s reduction mandate.

Moreover, many of our inhalation pipeline assets use HFCs subject to the AIM Act’s reduction mandate.

There can be no assurance that we will be able to acquire adequate supplies of HFCs for current and future commercialization of our products as a result of the AIM Act or other similar statutes and regulations.

Moreover, changes to the ingredients of our proprietary and generic products requires FDA approval and there can be no assurance that we will be able to obtain such approval or the timing of such approval.

ANP currently manufactures heparin sodium for our enoxaparin product, isoproterenol and hyaluronidase for Amphastar’s current products, and we plan to have ANP manufacture APIs and starting materials for APIs for certain other products and product candidates.

Sales and Marketing

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We face and will face significant competition for our products and product candidates from pharmaceutical companies that focus on the generic injectable and inhalation markets such as Pfizer, Inc., Eli Lilly and Co., Sagent Pharmaceuticals, Inc., Akorn, Inc., Sandoz Inc., Viatris Inc., Fresenius Kabi USA, Nexus Pharmaceuticals, Apotex Corp, Amneal Biosciences, American Regent Inc., Hikma Pharmaceuticals USA, Inc., Par Pharmaceuticals, Cipla USA Inc., Meitheal Pharmaceuticals, Dr.

Reddy’s Laboratories, Inc., Sun Pharmaceuticals, Inc., Accord Healthcare Ltd., Amring Pharmaceuticals, Bausch Health, Zydus Pharmaceuticals USA Inc., AuroMedics Pharma LLC, and Teva Pharmaceutical Industries Ltd.

Reddy’s Laboratories, Inc., Sun Pharmaceuticals, Inc., Accord Healthcare Ltd., Amring Pharmaceuticals, Bausch Health, Zydus

Pharmaceuticals USA Inc., AuroMedics Pharma LLC, and Teva Pharmaceutical Industries Ltd.

Competition in the generic pharmaceutical industry has increased as producers of branded products have entered the business by creating generic drug subsidiaries, purchasing generic drug companies, or licensing their products to generic manufacturers prior to patent expiration and/or as their patents expire.

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Sanofi also markets its authorized generic enoxaparin product through its subsidiary, Winthrop.

Fresenius Kabi USA, Apotex Corp., and Meithael Pharmaceuticals, Inc.

Fresenius Kabi USA, Apotex Corp., Zydus Pharmaceuticals USA Inc., Sandoz, and Meithael Pharmaceuticals, Inc.

also market a generic version of enoxaparin.

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For pharmaceutical companies, the most important competitive factors are scope of product line, ability to timely develop new products and relationships with group purchasing organizations, retailers, wholesalers and customers.

of generic pharmaceutical products tend to follow a pattern based on regulatory and competitive factors.

Sales of generic pharmaceutical products tend to follow a pattern based on regulatory and competitive factors.

As patents for brand-name products and related exclusivity periods expire, the first generic pharmaceutical manufacturer to receive regulatory approval for generic versions of products is typically able to achieve significant market penetration and higher margins.

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There are two drug approval processes under the FFDCA — an ANDA approval process for generic drugs and an NDA approval process for new drugs that cannot be approved in ANDAs.

process for biosimilar products that are approved based on their similarity to biologicals that were previously approved in BLAs.

For drugs that are “biological products” within the meaning of the PHSA, there are two different approval processes — a biological license application, or BLA, approval process for original biological products and a biosimilar application approval process for biosimilar products that are approved based on their similarity to biologicals that were previously approved in BLAs.

The ANDA Approval Process

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Applicants seeking to market such products can submit an NDA under Section 505(b)(2) of the FFDCA with supportive data from clinical trials.

The Generic Drug User Fee Act, or GDUFA, was enacted by Congress in 2012 and was reauthorized as GDUFA II in 2017.

The Generic Drug User Fee Act, or GDUFA, was enacted by Congress in 2012 and was reauthorized as GDUFA II in 2017 and GDUFA III in 2022.

GDUFA is designed to provide funding to the FDA to expedite timelines for the FDA’s review of ANDA applications.

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For example, as part of GDUFA II, the goal of the FDA is to complete the review of 90% of original ANDA applications within 10 months from filing of the ANDA.

Under the previous GDUFA authorization, the average time for sponsors to obtain FDA approval of ANDAs was 32-34 months post-filing.

Under previous GDUFA authorizations, the average time for sponsors to obtain FDA approval of ANDAs was 32-34 months post-filing.

As newer GDUFA reauthorizations occur in 5 year increments, it is expected that these ANDA timelines will also change.

Upon approval of an NDA or ANDA, the FDA lists the product in a publication entitled “Approved Drug Products with Therapeutic Equivalence Evaluations,” which is commonly known as the “Orange Book.” In the case of an NDA, the FDA also lists patents identified by the NDA applicant as claiming the drug or an approved method of using the drug.

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(3) the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration;

or (4) the patent is invalid or will not be infringed upon by the manufacture, use or sale of the drug product for which the ANDA is submitted.

or (4) the patent is invalid or will not be

infringed upon by the manufacture, use or sale of the drug product for which the ANDA is submitted.

This last certification is known as a Paragraph IV certification.

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Such a determination may affect an applicant’s first to file status and eligibility for 180-day exclusivity.

The Medicare Prescription Drug Improvement and Modernization Act of 2003, or the MMA, provides that the 180-day exclusivity delay ends 180 days after the first commercial marketing of

the ANDA product.

The Medicare Prescription Drug Improvement and Modernization Act of 2003, or the MMA, provides that the 180-day exclusivity delay ends 180 days after the first commercial marketing of the ANDA product.

This exclusivity may be forfeited under a number of different circumstances, including:

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This six-month exclusivity, which runs from the end of other exclusivity protection or patent delay, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued written request for such a study.

The FFDCA also provides exclusivity for certain antibiotic drugs for serious or life-threatening infections that FDA designates as “qualified infectious disease products.” This exclusivity extends other exclusivities for the same drug by five years, but does not extend patent-related delays in approval.

The FFDCA also provides exclusivity

for certain antibiotic drugs for serious or life-threatening infections that FDA designates as “qualified infectious disease products.” This exclusivity extends other exclusivities for the same drug by five years, but does not extend patent-related delays in approval.

In 2017, the FDA Reauthorization Act of 2017, or FDARA, was passed, which created a new pathway to allow the FDA to expedite the development and review of an ANDA for a drug that is designated as a Competitive Generic Therapy, or CGT.

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Like GDUFA, PDUFA must be reauthorized every 5 years.

It is currently authorized as PDUFA VI through September of 2022.

It is currently authorized as PDUFA VII through September of 2027.

As part of the PDUFA, the FDA has specific goals for reviewing NDA/BLA applications.

For example, as part of PDUFA VI, the goal of the FDA is to complete the review of 90% of original NDAs that are not new molecular entities within 10 months of the date of filing the NDA.

For example, as part of PDUFA VII, the goal of the FDA is to complete the review of 90% of original NDAs that are not new molecular entities within 10 months of the date of filing the NDA.

The approval process for a full NDA generally involves:

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Before human clinical trials can begin on a new drug, the results of preclinical tests, together with manufacturing information and analytical data, must be submitted to the FDA as part of an IND and the FDA must permit the IND to become effective.

Each clinical trial under an IND must be reviewed and approved by an independent Institutional Review Board, or IRB.

Each clinical trial under an IND must be reviewed and approved by an independent Institutional

Review Board, or IRB.

Human clinical trials are typically conducted in three sequential phases that may overlap.

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An applicant with a pending or approved biosimilar application may seek an FDA determination that its product is interchangeable with the reference drug.

In addition to demonstrating biosimilarity to the reference product, the biosimilar applicant must demonstrate that its product can be expected to yield the same clinical result as the reference product in any given patient.

In addition to demonstrating biosimilarity to the reference product, the

biosimilar applicant must demonstrate that its product can be expected to yield the same clinical result as the reference product in any given patient.

If the biosimilar product may be administered more than once to a patient, the applicant must demonstrate that the risk in terms of safety or diminished efficacy of alternating or switching between the biosimilar and reference products is not greater than the risk of continued administration of the reference product.

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It also precludes exclusivity for an entirely new BLA in certain circumstances.

A new BLA submitted by a sponsor or manufacturer of a previously approved biologic

would not be protected by exclusivity for (1) a non-structural change that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or strength or (2) a structural change that does not result in a change in safety, purity or potency.

A new BLA submitted by a sponsor or manufacturer of a previously approved biologic would not be protected by exclusivity for (1) a non-structural change that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or strength or (2) a structural change that does not result in a change in safety, purity or potency.

As in the case of NDAs approved under the FFDCA, BLAs may be entitled to orphan exclusivity and to pediatric exclusivity.

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NDAs are reviewed by personnel within the Center for Drug Evaluation and Research, or CDER, while device applications and premarket notifications are reviewed by the Center for Devices and Radiological Health, or CDRH.

When reviewing a drug/device combination product, the FDA must assign a lead Center to review the product, based on the combination product's primary mode of action, or PMOA, which is the single mode of a combination product that provides the most important therapeutic action of the combination product.

For biologic products, the BLAs are generally reviewed by personnel within the Center for the Biologic Evaluation and Research, or CBER.

When reviewing a drug (biologic)/device combination product, the FDA must assign a lead Center to review the product, based on the combination product's primary mode of action, or PMOA, which is the single mode of a combination product that provides the most important therapeutic action of the combination product.

The Center that regulates that portion of the product that generates the PMOA becomes the lead evaluator.

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If multiple applications are submitted, each may be evaluated by a different lead Center.

● O ur inhalers and prefilled syringes, which deliver a specific drug, are regulated by the FDA as combination products.

We believe the combination products will be regulated by the FDA as a drug (and not a device) because the primary mode of action of the combination will be a drug action.

As such, we will need to submit a marketing application to the CDER for our inhalers or prefilled syringes that deliver a specific drug.

CDRH will provide input to CDER on the device aspects of the combination.

● O ur inhalers and prefilled syringes, which deliver a specific drug or biologic, are regulated by the FDA as combination products.

We believe the combination products will be regulated by the FDA as a drug or biologic (and not a device) because the primary mode of action of the combination will be a drug (or biological) action.

As such, we will need to submit a marketing application to the CDER (or CBER) for our inhalers or prefilled syringes that deliver a specific drug.

CDRH will provide input to CDER (or CBER) on the device aspects of the combination.

We can provide no assurance that any of our combination products will be approved by FDA in a timely fashion, if at all.

● L ike their constituent products—e.g., drugs and devices—combination products are highly regulated and subject to a broad range of post marketing requirements including cGMPs, adverse event reporting, periodic reports, labeling and advertising and promotion requirements and restrictions, market withdrawal and recall.

● L ike their constituent products—e.g., drugs/biologics and devices—combination products are highly regulated and subject to a broad range of post marketing requirements including cGMPs, adverse event reporting, periodic reports, labeling and advertising and promotion requirements and restrictions, market withdrawal and recall.

FDA Action on an Application for Approval

If applicable statutory or regulatory requirements are not satisfied, the FDA may deny approval of an NDA, ANDA, BLA, or biosimilar application, or the FDA may require additional data or information.

After approval of the application, the FDA may suspend or withdraw the approval based on various criteria, including new information related to safety or effectiveness or failure to comply with post-approval requirements.

After approval of the application (or license), the FDA may suspend or withdraw the approval based on various criteria, including new information related to safety or effectiveness or failure to comply with post-approval requirements.

In addition, the FDA may in some instances require post-marketing studies on approved products and may take actions to limit marketing of the product based on the results of those studies.

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Success in early stage clinical trials does not assure success in later stage clinical trials.

Data obtained from clinical activities are not always conclusive and may be subject to varying interpretations that could delay, limit or prevent regulatory approval.

obtained from clinical activities are not always conclusive and may be subject to varying interpretations that could delay, limit or prevent regulatory approval.

Even if a product receives regulatory approval, later discovery of previously unknown problems with a product may result in restrictions on the product or complete withdrawal of the product from the market.

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Maintaining substantial compliance with appropriate federal, state and local statutes and regulations requires the expenditure of substantial time and financial resources.

Drug manufacturers are required to register their establishments with the FDA and certain state agencies.

Drug and biologic manufacturers are required to register their establishments with the FDA and certain state agencies.

After approval, the FDA and these state agencies conduct periodic unannounced inspections to ensure continued compliance with ongoing regulatory requirements.

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The FDA may require post-approval testing and surveillance programs to monitor safety and effectiveness of approved products that have been commercialized.

Any drug products manufactured or distributed pursuant to FDA approvals are subject to continuing regulation by the FDA, including:

Any drug or biologic products manufactured or distributed pursuant to FDA approvals are subject to continuing regulation by the FDA, including:

● record-keeping requirements;

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There are numerous regulations and policies that govern various means for disseminating information to health-care professionals, as well as consumers, including industry sponsored scientific and educational activities, information provided to the media and information provided over the Internet.

Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label.

Drugs or biologics may be promoted only for the approved indications and in accordance with the provisions of the approved label.

FDA Enforcement Authority

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The FDA has authority to inspect manufacturing facilities as well as other facilities in which drug products are held, packaged or stored, to determine compliance with cGMP and other requirements under the FDCA.

The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to

have improperly promoted off-label uses may be subject to significant liability.

In addition, even after regulatory approval is obtained, later discovery of previously unknown problems with a product may result in restrictions on the product or even complete withdrawal of the product from the market.

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In April 2020, the FDA granted approval of our Epinephrine Injection USP 30mg/30mL Multiple Dose Vial.

Additionally, the FDA granted approval of our ANDAs for atropine sulfate injection, dextrose injection and morphine sulfate injection in October 2020, March 2021 and April 2021, respectively.

Additionally, the FDA granted approval of our ANDAs for atropine sulfate injection, dextrose injection, morphine sulfate injection, and epinephrine injection single dose prefilled syringe in October 2020, March 2021, April 2021, and August 2022, respectively.

The FDA has adopted a risk-based enforcement policy that prioritizes enforcement of new drug requirements for these and other unapproved drugs that pose safety concerns, lack evidence of efficacy, prevent patients from pursuing effective therapies, are marketed fraudulently, violate other provisions of the FFDCA, such as cGMP requirements, or directly compete with approved drugs.

The FDA has indicated that approval of an NDA for one drug within a class of drugs marketed without FDA approval may trigger agency enforcement of the new drug requirements.

Once the FDA issues an approved NDA for one of the drug products at issue or completes the efficacy review for that drug product, it may require other manufacturers to also obtain approval for that same drug in order to continue marketing it in the United States.

Once the FDA issues an

approved NDA for one of the drug products at issue or completes the efficacy review for that drug product, it may require other manufacturers to also obtain approval for that same drug in order to continue marketing it in the United States.

While the FDA generally provides sponsors a one-year grace period, the agency is not statutorily required to do so.

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The Open Payment Act

The Physician Payment Sunshine Act, or the Open Payment Act, which was enacted as part of the Affordable Care Act, requires all pharmaceutical manufacturers that participate in Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the Secretary of the Department of Health and Human Services payments or other transfers of value made in the previous year by that entity, or by a third party as directed by that entity, to covered recipients, including physicians (defined to include doctors of medicine and osteopathy, dentists, podiatrists, optometrists, and licensed chiropractors), certain non-physician healthcare professionals (such as physician assistants and nurse practitioners, among others), and teaching hospitals, as defined by law, or to third parties on behalf of such covered recipients, as well as ownership and investment interests held by physicians and their immediate family members.

recipients, as well as ownership and investment interests held by physicians and their immediate family members.

The payments and transfer of value required to be reported include the cost of meals provided to a physician, travel reimbursements and other transfers of value provided as part of contracted services, including speaker programs, advisory boards, consultation services and clinical trial services.

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As a life sciences company, we are subject to the federal anti-kickback statute, or AKS.

The AKS prohibits payments or providing anything of “value” (remuneration) for the purpose of inducing or rewarding the referral or generation of

healthcare business.

The AKS prohibits payments or providing anything of “value” (remuneration) for the purpose of inducing or rewarding the referral or generation of healthcare business.

The intent is to protect the independence and clinical judgment of providers.

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For example, as a result of environmental concerns about the use of CFCs, the FDA issued a final rule on January 16, 2009 that required the phase-out of the CFC version of our Primatene MIST ® product by December 31, 2011.

This phase out caused us to halt sales of the CFC version of our Primatene MIST ® product subsequent to December 31, 2011 and write off our inventory for the product, which had an adverse effect on our financial results.

This phase out caused us to halt sales of

the CFC version of our Primatene MIST ® product subsequent to December 31, 2011 and write off our inventory for the product, which had an adverse effect on our financial results.

Similarly, on December 27, 2020, the American Innovation in Manufacturing Act of 2020, or AIM Act, was enacted.

The AIM Act directs the United States Environmental Protection Agency to address usage of hydrofluorocarbons, or HFC, by reducing production and consumption of certain HFCs.

Many of our products, including Primatene MIST ® , utilize HFCs subject to the AIM Act’s reduction mandate.

One of our products, Primatene MIST ® , utilizes HFCs subject to the AIM Act’s reduction mandate.

Moreover, many of our inhalation pipeline assets use HFCs subject to the AIM Act’s reduction mandate.

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Of these employees, 21 hold Ph.D.’s, and an additional 116 employees hold a master’s degree or other post-graduate degrees.

We consider our employees’ intellectual capital to be an essential driver of our business and key to our future prospects.

We consider our employees’ intellectual capital an essential driver of our business and key to our future prospects.

None of our U.S.

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Our talent acquisition team uses internal and external resources to recruit highly skilled candidates globally.

We continue to attract and retain superior talent as measured by our minimal turnover rate and high employee service tenure.

Total Rewards

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We provide employees with compensation packages that include base salary, annual incentive bonuses, and long-term equity awards.

We also provide comprehensive employee benefits, which vary by country and

region, such as life and health insurance, health savings accounts, paid time off, an Employee Stock Purchase Program, and a 401(k) plan.

We also provide comprehensive employee benefits, which vary by country and region, such as life and health insurance, health savings accounts, paid time off, an Employee Stock Purchase Program, and a 401(k) plan.

Health, Safety, and Wellness

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These programs are highlighted regularly in our monthly human resources newsletters.

These investments and the prioritization of employee health, safety, and wellness were particularly significant in 2021 in light of the ongoing COVID-19 pandemic.

To protect and support our essential team members, we implemented health and safety measures that included maximizing personal workspaces, changing shift schedules, providing personal protective equipment, or PPE, implementing heightened cleaning of high contact surfaces, and instituting mandatory screening before accessing buildings.

These investments and the prioritization of employee health, safety, and wellness were particularly significant in 2021 and 2022 in light of the ongoing COVID-19 pandemic.

To protect and support our essential team members, we implemented and/or trained employees on health and safety measures that included maximizing personal workspaces, changing shift schedules, providing personal protective equipment, or PPE, implementing heightened cleaning of high contact surfaces, and instituting mandatory screening before accessing buildings.

We notify employees of exposure and close contacts and offer COVID-19 testing after potential exposure.

We will continue to monitor this evolving situation and will continue to seek programs to educate and assist employees whenever possible.

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Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, are available free of charge as soon as reasonably practicable after we electronically file them with, or furnish them to, the SEC.

You can access our filings with the SEC by visiting www.amphastar.com.

The information that is contained on or that can be accessed through our website is not incorporated into this Annual Report on Form 10-K, and the inclusion of our website address is an inactive textual reference only.

Additionally, copies of materials filed by us with the SEC may be accessed at the SEC’s website at www.sec.gov.

You can access our filings with the SEC by visiting http://www.amphastar.com.

The SEC also maintains an Internet website that contains reports, proxy statements and other information about issuers, like us, that file electronically with the SEC.

The address of that website is http://www.sec.gov.

We use our website as a channel of distribution for important company information.

Important information, including press releases, analyst presentations and financial information regarding us, as well as corporate governance information, is routinely posted and accessible on the “Investors” section of the website, which is accessible by clicking on the tab labeled “Investors” on our website home page.

Information on or that can be accessed through our website is not part of this Annual Report on Form 10-K, and the inclusion of our website address is an inactive textual reference only.

The contents of the websites provided above are not intended to be incorporated by reference into this Annual Report on Form 10-K or in any other report or document we file with the SEC.

Further, our reference to the URLs for these websites are intended to be inactive textual references only.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business