Drugs

Overview of Drugs

The Federal Food Drug and Cosmetic Act (FDCA) and the Food and Drug Administration (FDA) regulations define the term drug, in part, by reference to its intended use, as an article “intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “intended to affect the structure or any function of the body of man or other animals.” Therefore, products claiming to do any of these will be regulated by FDA as a drug, whether ingested, applied topically, or injected.

There are many FDA requirements that apply to drugs that do not apply to foods, dietary supplements or cosmetics. However, the degree of FDA regulation depends upon the class of drug. Over the counter (OTC) monographs and Homeopathic Pharmacopeia face less stringent requirements than other types of drugs.

Before sale in or importation into the U.S. all drugs must be:

1. Established as safe and effective for their intended uses;
2. Properly formulated, and not adulterated;
3. Properly labeled, and marketed within established FDA regulations;
4. And manufactured, processed, packed, and labeled in facilities that are registered.

FDA inspectors regularly stop and examine imported drug shipments. Drugs that are not in compliance with all FDA regulations or are from unregistered drug facilities will be subject to detention, import alerts, and refusal of admission.

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Registration & Listing

Facilities that manufacture, prepare, propagate, compound, process, or label drugs intended for sale in the US must be registered with FDA, including listing all drugs produced or modified at these facilities. Foreign establishments must also identify a U.S. agent and importers when registering. Drug manufacturers must submit registration information for their establishments, submit listing information, and update their information before December 31^st of every year.

FDA also requires annual reporting by drug registrants for listed drug and biological products manufactured, prepared, propagated, compounded, or processed for commercial distribution.

FDA uses registration to monitor drugs after entering the market, track drug availability, assess fees, and identify unapproved drugs. Facilities are registered with FDA’s online registration system. Many companies find the new FDA registration and listing processes difficult to manage, even those which were registered in the past. Read more about registration and listing.

Labeling & Claims

Whether FDA considers a product to be a drug is based on its intended use. FDA determines an article’s intended use primarily through labeling and advertising or marketing. Information on websites selling FDA regulated products is considered labeling for FDA purposes and advertising for the Federal Trade Commission (FTC) purposes. What FDA regulation requires to appear on a drug label depends upon the regulatory classification of the drug. Specific types of drugs all have their own labeling requirements, including prescription (Rx), APIs, OTC, and homeopathic drugs. Whether a drug is topical, injectable, or oral impacts the labels. Labeling is a commonly detected flaw, and incorrect labels when importing can lead to detention, import alerts, and import refusal.

Claims can appear on the product itself or in advertising or marketing. Drug claims imply or explicitly state that a product is beneficial for treating, mitigating, or preventing disease or otherwise affecting the structure or functions of the human body. Some examples are claims that products will restore hair growth, reduce cellulite, and or reduce or remove wrinkles. If FDA perceives something as a drug claim, a product can suddenly be considered an unapproved drug, even if the manufacturer intended it to be a supplement or cosmetic. Products that meet both the cosmetic and drug definitions are regulated as both, including creams and lotions claiming to have sun protection factor (SPF) benefits, dandruff shampoos, antiperspirants, hand sanitizers, toothpastes, mouthwashes, and others. This means they must meet both cosmetic and drug requirements.

Ensuring that products are correctly labeled and do not make inaccurate or undesired claims can make a huge difference in getting these products into the US market. Read more about labeling, or about claims.

Good Manufacturing Practices (GMPs)

As part of FDA’s requirement for Standard Operating Procedures (SOPs) and quality controls, their regulations also require that all drugs be manufactured in accordance with FDA’s Good Manufacturing Practice (GMPs) regulations. Proper manufacturing of a drug product is as important as proper drug formulation and product drug design. Failure of a manufacturer to comply with FDA’s drug GMPs renders the manufactured drugs adulterated under the Federal Food Drug and Cosmetic Act (FDCA) and FDA regulations.

FDA often seizes drugs that were manufactured out of drug GMP compliance. If FDA determines that a foreign drug manufacturer is failing to comply with FDA’s drug GMPs, the agency will place the foreign drug manufacturer on an FDA Import Alert. Future drug importations from that drug manufacturer will be subject to FDA import detentions and FDA import refusals. This results in FDA blocking and automatically detaining imported drug shipments from that drug manufacturer until the drug GMP compliance problems are solved (and documented for FDA review).

Foreign facilities which do not follow FDA’s GMP can have their goods detained, placed on an import alert, or refused.

Recalls

A recall is a voluntary action taken by a company at any time to remove a defective drug product from the market. FDA considers drug recalls to be the most effective way to protect the public from a defective or potentially harmful product. A company may initiate its own recall, or FDA may request one. FDA oversees recalls, assesses their effectiveness, and classifies them. Recalls can be extremely costly, but most problems requiring recalls are preventable. Read more about recalls here.

APIs & Bulk Ingredients

An Active Pharmaceutical Ingredient (API) is an ingredient in a finished drug that has the intended therapeutic effect. FDA regulates all drug components as drugs, but APIs face greater scrutiny than inactive ingredients, especially their quality and purity. When a chemical is classified as an API, it is subject to FDA’s good manufacturing practices (GMP) regulations.

FDA has concluded that APIs cannot be legally labeled except under specific exemptions:

• in clinical trials,
• as an ingredient in an approved drug,
• for pharmacy compounding,
• for chemical testing, for research and analysis,
• for law enforcement,
• and for training and teaching.

APIs face the same facility registration, listing, and labeling requirements as other drugs.

Compounding

Drug compounding is the process of combining, mixing, or altering ingredients to create a medication tailored to the needs of an individual patient. Compounding commonly occurs in pharmacies, although it may also occur in other settings, and it is often conducted using active pharmaceutical ingredients (APIs).

FDA does not approve, verify the safety, or efficacy, or quality of compounded drugs before they enter the market. In the past FDA has caught compounders making false and misleading statements that compounded drugs are safe and effective, sometimes for the treatment of serious diseases, by incorrectly suggesting the drugs had met the standard for FDA approval.

In 2012, a single compounding pharmacy led to more than 750 cases of infection and more than 60 deaths of patients in 20 states from fungal meningitis. Since then, FDA has found many serious patient illnesses and deaths linked to poor quality compounded drugs.

Federal law addresses compounding by a licensed pharmacist in a state-licensed pharmacy, or federal facility, or by a physician, as well as compounding by or under the direct supervision of a licensed pharmacist in an outsourcing facility. Quality requirements for compounded drugs differ depending on the setting where compounding occurs.

Outsourcing facilities that compound drugs are subject to current good manufacturing practice (cGMP) requirements and FDA inspections. Drugs compounded by pharmacists or physicians are subject to the less stringent standards of section 503A of the Food Drug & Cosmetic Act, as well as licensing and other state-level regulations.

Regardless of where compounding occurs, some federal requirements apply, including sanitary conditions for preparation, packing, and storage. Recent years have seen substantial litigation in the field of pharmacy compounding, all the way up to the Supreme Court.

New Drugs

New drugs are defined by those that were first marketed in the U.S. after 1938, which accounts for almost all drugs currently on the market. FDA determines if a new drug should enter the U.S. market using a new drug application (NDA), or an abbreviated new drug application (ANDA) for generics.

NDAs:

• Include data from clinical trials and animal studies, information about drug ingredients and their effects, and details about the manufacturing process. FDA uses the NDA to determine: if the new drug is safe and effective in its proposed use, what kind of labeling is appropriate, and if the manufacturing methods and quality controls used are adequate.

ANDAs:

• Include data that supports the review and ultimate approval of a generic drug product. These applications are called “abbreviated” since they do not have to include preclinical (animal) and clinical (human) data to prove safety and effectiveness. FDA uses the ANDA to decide if the product performs in the same manner as the original drug. Once approved, an applicant may manufacture and market the generic drug product to supply a safe, effective, low-cost alternative to the public.

Over-the-Counter (OTC) Drugs

Over-the-counter (OTC) drugs are medicines that may be sold directly to a consumer without a prescription from a doctor. In the U.S., OTC drugs are usually regulated based upon their active pharmaceutical ingredients (APIs), rather than their final formulation. This allows manufacturers freedom to formulate ingredients into proprietary mixtures within the scope of broad regulatory requirements.

OTC monographs allow manufacturers to bypass the high standard of an NDA for certain types of OTC drugs. These monographs state specific requirements for categories of non-prescription drugs, such as what ingredients may be used for what purposes. New drugs that fulfill the requirements of an OTC monograph can make it to the U.S. market much more quickly and easily. However, this does not exempt OTC drugs from labeling and claims regulations.

Homeopathic Drugs

FDA regulates homeopathic products as homeopathic drugs. While homeopathic drugs are subject to most of the same FDA regulatory requirements as other drugs, the FDCA established the Homeopathic Pharmacopoeia of the United States (HPUS) as a legal standard and authority for establishing drug quality and compliance. HPUS provides a set of standards for the manufacturing and labeling of homeopathic drugs, including monographs. Because of this apparent conflict between the HPUS and the FDA regulations, FDA issued a homeopathic drug Compliance Policy Guide (CPG) that identifies specific conditions under which homeopathic drugs may ordinarily be marketed without a new drug application approval. Wherever an HPUS requirement conflicts with FDA regulations without an explicit exemption, FDA regulations apply.

Because homeopathic drug dosages are based on principles of serial dilution (attenuation), homeopathic products must be labeled to indicate the number of dilutions that the substance has undergone.  Homeopathic drugs may be OTC drugs or prescription drugs depending upon whether they are intended for use in self-limiting disease conditions amenable to self-diagnosis.

If a homeopathic drug complies with an HPUS monograph, is correctly labeled, is manufactured in a registered establishment, and is listed, it can be marketed in the US without FDA approval, even if it is a prescription drug. Drugs classified as homeopathic can even make certain lawful drug claims and fit into growing US market trends towards favoring natural and organic products.

Failing to comply with the HPUS, FDA regulations, and the FDA CPG can lead to classification an unapproved, misbranded, or adulterated drug. This can result in FDA import detention, import alerts, and refusal of admission.

Need Help?

FDAImports represents many domestic and foreign drug manufacturers, processors, packers, labelers, importers, and distributors. Our client base includes large and small branded drug and generic drug companies, finished drug and active pharmaceutical ingredient (API) companies, OTC, homeopathic and FDA approved prescription drug companies, and companies involved in performing clinical trials in the United States and around the world.

We specialize in helping foreign drug companies obtain and maintain clear drug supply chains from their foreign manufacturing and distribution sites to the US. market. Importing drugs into the United States brings unique challenges and FDAImports is uniquely suited to make The Way Through clear and efficient. Contact us today for assistance.