1.1 Legislation and Regulation for Pharmaceuticals and Medical Devices

The primary legislation governing the authorisation, marketing, sale and supply of pharmaceutical products by the US Food and Drug Administration (FDA) is the Federal Food, Drug, and Cosmetic Act (FD&C Act), which has been amended many times over the years to reflect increasing FDA mandates for the regulation of pharmaceutical products. The Public Health Service Act (PHS Act) is the specific authority utilised to approve or license biologic (including biosimilar) products. The primary FDA regulations governing drugs and biologics are found at Chapter 21 of the Code of Federal Regulations. Controlled substances, such as opioids, are also scheduled, and subject to quotas and distribution controls, under the Controlled Substances Act administered by the Drug Enforcement Administration (DEA).

A drug is defined as:

  • a substance recognised in the US Pharmacopoeia, Homeopathic Pharmacopeia or National Formulary;
  • a substance intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease;
  • a substance (other than food) intended to affect the structure or any function of the body;
  • a substance intended for use as a component of a drug, but not a device or a component, part or accessory of a device.

A biologic is defined under the PHS Act as "a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings". Biological products are also included within the drug definition and are generally covered by most of the same laws and regulations, but differences exist in the regulatory approach, particularly with respect to manufacturing processes.

Medical devices are also regulated by the FDA under the FD&C Act, and, although subject to similar intent standards, such products generally are primarily intended to act via mechanical rather than chemical or biological modes of action. Medical devices are classified by risk, and may be exempt from FDA review, subject to a "510(k)" pre-market notification process based upon a showing of substantial equivalence to a "predicate" device, subject to down-classification via the de novo submission process, or eligible for full approval via a pre-market approval application (PMA).

Although the FDA has traditionally been given significant independence as an agency, and the Commissioner is confirmed by the Senate, the FDA is part of the Department of Health and Human Services (HHS).

The government agencies touching on pricing and reimbursement vary, depending upon the payer programme, and include the Centers for Medicare & Medicaid Services (CMS) (also part of HHS), the Veterans Health Administration, and state Medicaid agencies. In addition, the HHS Office of Inspector General oversees laws governing fraud and abuse in the sale of biomedical products and healthcare services. The Federal Trade Commission (FTC), an independent agency, regulates the advertising of non-prescription drugs and non-restricted medical devices.

1.2 Challenging Decisions of Regulatory Bodies That Enforce Pharmaceuticals and Medical Devices Regulation

Agency decisions may be challenged either informally, via guidance-driven processes governing informal dispute resolution, or via more formal regulatory processes specified under FDA regulations. In addition, a general-purpose vehicle for bringing issues before the agency is the Citizen Petition, which allows the petitioner to bring a request before the agency and initiate a public docket in which comments can be lodged. The FDA also maintains ombudsmen in the various centres reviewing products, whose role is intended to facilitate the resolution of disputes. Although procedures for dispute resolution vary by the specific statutory provisions at issue and the FDA Center responsible for the category of products, such processes generally follow APA standards for permitting due process and creation of an administrative record.

Once administrative processes are exhausted, parties with appropriate standing may challenge FDA agency decisions in court under the Administrative Procedure Act (APA). Although administrative processes vary by category, APA requirements are largely the same across products, and typically involve a demonstration that an agency action was arbitrary or capricious or otherwise not in accordance with governing law.

1.3 Different Categories of Pharmaceuticals and Medical Devices

Although the default for drug approvals is technically over-the-counter (OTC), ie, non-prescription, status, most initial drug approvals specify that new drug products are subject to prescription drug controls. Prescription drugs must be labelled as such and are subject to physician prescribing and pharmacy dispensing and substitution controls under state law.

However, it is possible to seek an initial FDA approval for the sale of a drug product OTC, or seek to "switch" a prescription product to OTC status by demonstrating that the condition is capable of self-diagnosis and treatment in accordance with labelling. Moreover, over the decades, the FDA has also developed OTC monographs that permit the marketing, without approval, of certain OTC drugs that meet the specific terms - ingredients, dosing, directions for use, etc - for that class of drug under the relevant monograph. Such drugs remain subject to establishment registration, listing, labelling and current Good Manufacturing Practice (cGMP) requirements. Currently pending legislation may liberalise the processes for amending OTC monographs and provide incentives that could reinvigorate OTC product development in the US.

Medical devices may also be restricted to non-restricted (including OTC) or restricted status, depending on their classification and the FDA's determination as to appropriate status under clearance and approval processes.


2.1 Regulation of Clinical Trials

For drugs and biologics, unless subject to specific exemptions, an investigational new drug application (IND) must be submitted to obtain FDA clearance prior to engaging in clinical research. Such submissions typically include extensive pre-clinical data, information on chemistry, manufacturing and controls, prior human data and the proposed protocol(s). The FDA has 30 days either to allow the clinical study to proceed or to impose a clinical hold until outstanding issues are resolved. Similar rules apply to medical device research and, depending upon the risk posed by the device, a device study may require the submission of an investigational device exemption (IDE) prior to initiating clinical research. Nonsignificant risk device studies may be conducted with just Institutional Review Board (IRB)/Ethics Committee approval. The FDA maintains an array of good clinical practice regulations governing clinical research, including study sponsor, IRB, and investigator responsibilities.

2.2 Procedure for Securing Authorisation to Undertake a Clinical Trial

As noted, in addition to obtaining approval to proceed with clinical research by filing an IND or IDE, as appropriate, virtually all studies must be reviewed by one or more IRBs prior to initiation. FDA regulations specify the requirements applicable to the composition and activities of IRBs.

2.3 Public Availability of the Conduct of a Clinical Trial

The US National Institutes of Health maintains a database at www.clinicaltrials.gov, and most controlled, interventional clinical investigations, other than Phase I clinical investigations, of drugs or biologic products subject to FDA regulation, must be registered with the site. The clinicaltrials.gov database has greatly expanded the obligation to include more expansive results information. While there is no general requirement to publish clinical trial data in journals, as a practical matter the industry has pledged to seek such publications where possible.

2.4 Restriction for Using Online Tools to Support Clinical Trials

Online tools may be used as long as they comply with applicable requirements (eg, privacy, data security, informed consent and other good clinical practice requirements, and establishing lawful status if such tools incorporate certain regulated medical device functionalities). Particular requirements apply to recruiting subjects for clinical studies, and advertisements for study subjects, whether online or otherwise, must be IRB-approved and limited to basic information.

2.5 Use of Resulting Data from the Clinical Trials

The personal data resulting from clinical trials would be considered protected, although in certain scenarios the sponsor and the FDA will have access to such information, including patient-identifiable information, in order to conduct and analyse the data from the study properly.

As long as any transfer of resulting data to a third party or an affiliate is consistent with contractual obligations, informed consent, and privacy protections, such transfers are permitted.

2.6 Databases Containing Personal or Sensitive Data

A database containing personal or sensitive data may be subject to both contractual and statutory protections obliging maintenance of data security and privacy. Such data is also typically protected under the Freedom of Information Act, to the extent it has been submitted to a US government agency

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Originally published by Chambers GLOBAL PRACTICE GUIDES

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