FAQs About Manufacturing Quality

CHPA member companies continuously monitor the quality and manufacturing processes of their over-the-counter (OTC) medicines. Companies use science- and risk-based methods to assess the quality of each drug component and of the final product. The methods utilized are based on U.S.-accepted guidelines, guidances, or standards developed by the U.S. Food and Drug Administration (FDA) or by the U.S. Pharmacopeia (USP). In addition, many companies have adopted international quality guidelines developed by a corroborating body known as the International Conference on Harmonization. Companies also develop internal standard operating procedures (SOPs) to streamline their internal processes to establish an enhanced level of quality.

Guidelines, analytical standards, and standard operating procedures (SOPs) are an integral part of a pharmaceutical company’s core operation. FDA requires that companies use extensive Good Manufacturing Practices (GMPs) which provide constant measures to detect problems or undesired variations during the manufacturing process itself. With quality built into the manufacturing process, the GMPs allow for timely corrective action to take place at intermediate stages as opposed to solely quality testing of the final product alone. All CHPA member companies follow GMPs.

USP is a non-governmental, official public standards-setting authority for prescription and over-the-counter medicines manufactured or sold in the United States. Standards of quality, purity, identity, and strength for more than 4,000 active pharmaceutical ingredients (APIs), dosage forms, and excipients have been developed by USP. FDA’s regulatory authority includes enforcement of USP’s official standards for drugs imported to or marketed in the United States.

ICH is made up of the regulatory authorities and pharmaceutical industry members from three major regions: the United States, Japan, and the European Union. This body promotes Good Manufacturing Practices, pharmaceutical development, quality risk management, and pharmaceutical quality systems through collaboration on guideline development. ICH also provides guidelines on stability, analytical procedures, impurity testing, and specifications.

All CHPA member companies have developed internal SOPs to create repetitive and routine activities which facilitate reliable and unvarying conformance to quality standards and technical requirements.

GMPs spell out FDA’s extensive requirements that manufacturers must follow. Because FDA recognizes the need to encourage innovation and the development of improved manufacturing technologies, in some areas FDA offers manufacturers latitude to determine how to achieve the level of control necessary for GMP compliance. A manufacturer must document how its specific processes meet GMP standards.

GMPs set standards for manufacturing and testing:

• Raw materials quality assurance
• Record-keeping of substances throughout the manufacturing process
• Standards for cleanliness and safety
• Qualifications of manufacturing personnel
• In-house testing
• Production and process controls
• Warehousing and distribution

Yes. Quality testing is an integral part of the manufacturing process. Pharmaceutical companies have adopted ICH and FDA’s call for building quality into their pharmaceutical system at various stages of production rather than simply testing the final product. Final product testing, however, does occur in addition to testing throughout the manufacturing process.

CHPA member companies first determine the required material specifications for the items that go into making a product, and then perform due diligence to identify and qualify suitable suppliers. This process can include steps such as completion and review of supplier questionnaires; review of external audit reports; testing of critical product parameters; site audits; review of registration information as required; and scale up, stability, and validation as appropriate. In many cases, a company will choose a supplier where there is an existing relationship; building a trustworthy supplier relationship is regarded as one of the most important aspects of supplier quality assurance. 

Once a company begins receiving drug components from a supplier, it has and follows written procedures for receipt, handling, sampling, and testing of components. No lot of components can be used until the manufacturer’s quality control unit has sampled, tested, or examined it, and then released it for use.

As the industry’s regulating body, FDA is charged with performing inspections of foreign and domestic companies that manufacture pharmaceutical ingredients and excipients as well as the manufacturers of the final products. These audits are a means for an outside source to verify GMP compliance and quality. Additionally, FDA has a range of enforcement tools to ensure compliance.

All drug establishments, both domestic and foreign, must register with FDA if they have drugs in U.S. commerce. Drug establishments must list their drugs and provide national drug code numbers and registration numbers of other establishments within the parent company where the drug was manufactured or processed. Manufacturers are required to update these lists twice a year.

U.S. drug laws and enforcement applies to all drugs sold in the U.S. The laws are the same whether or not the drug is manufactured in the U.S. or elsewhere. U.S. drug laws require cooperation between U.S. Customs and Border Protection and the FDA on sampling of imports at the request of FDA.

In many cases, the process is the same. Companies focus on building a trustworthy relationship between the drug component supplier and the manufacturer to help prevent intentional and accidental adulteration. Auditing a supplier can help to provide a company with assurance that the supplier will act in accordance to the supplier/manufacturer agreement that is in place. In addition, companies perform their due diligence as part of their supplier qualification process which will help identify those suppliers that maintain public health and safety as a key priority. Companies also have an arsenal of tools and activities that can help prevent economic adulteration or counterfeiting, such as testing methodologies, additional auditing techniques, and methods for determining authentication of supplier documentation and records.

The systematic approach to product development uses sound science and quality risk management as well as in process testing to identify weaknesses or inadequacies in quality. The approach of building quality into the development process allows for real-time adjustments and early detection of quality problems. If a quality problem has been detected, a pharmaceutical firm stops production, evaluates the problem to determine the cause, evaluates the associated risks, and alters the process or supplier as deemed necessary.