503B has a genesis in the law on food, drugs and cosmetics

Establishments play a key role in healthcare due to their bulk production, strict quality standards and wide distribution.

The Drug Quality and Safety Act (DQSA) was established in 2013 in response to injections of contaminated steroids intended for intrathecal use that had caused an outbreak of fungal meningitis.1

The outbreak has infected 753 confirmed people and resulted in the deaths of 64.2 The contaminated steroid injections were manufactured by the New England Compounding Center. Title I of the DQSA, the Compounds Quality Act, amends the Federal Food, Drug and Cosmetic Act with respect to the preparation of medicinal products. From this amendment came article 503B.3

503B outsourcing facilities can produce large quantities of drugs for distribution to clinics, doctor’s offices and health care centers, with or without a prescription, while 503A pharmacies produce limited quantities of anticipatory preparations and patient-specific drugs. . 503B establishments are subject to more stringent regulations than traditional 503A dispensing pharmacies. Registration with the Drug Enforcement Administration, FDA, and State Boards of Pharmacy is a requirement for 503B outsourcing facilities, as well as compliance with General Chapters of the United States Pharmacopoeia (USP) , and current good manufacturing practices (cGMP) (21 Code of Federal Regulations, parts 210 and 211).

503B facilities are also subject to inspection by the FDA. CGMP regulations define the minimum requirements necessary during the processing, testing, packaging and distribution of pharmaceutical products.4 To comply with cGMP, the facilities establish a quality system, which provides the structure to ensure product quality and safety.5 An important aspect of a quality system is an independent quality unit that is responsible for creating procedures, investigating discrepancies, reviewing records, and ultimately approving and releasing or rejecting records. composite products (see figure).

A quality system is a control and balance system in which the quality unit oversees all aspects of a 503B outsourcing facility, from incoming raw materials to outgoing
of the final product. In addition to having an independent quality unit, there are many other critical aspects of a quality system in a 503B installation, including standard operating procedures (SOP), which provide clear and consistent instructions for performing tasks. .

503B establishments are required to have SOPs for preparing drug products and performing the myriad of other activities performed under the quality system. SOPs eliminate or reduce ambiguity in installation processes and are a key tool in personnel training.

Release of raw materials and supplies

The release of raw materials and supplies confirms the identity and quality of the raw materials used in the drug preparation processes. Raw material samples are taken and tested to ensure they meet predetermined specifications before use. Certificates of Analysis are obtained for each batch of components and raw materials to ensure they meet quality standards and specifications. Environmental monitoring of air cleanliness standards exists in the 503B facilities, so the facilities are designed to minimize the level of contaminants, thereby preventing microbiological contamination of pharmaceuticals.

Regular environmental testing is necessary to ensure the cleanliness of the drug preparation areas. International Organization for Standardization (ISO) 5 zones are tested at least every shift of production, while ISO zones 7 or 8 should be tested at least once a week to ensure that air cleanliness requirements are met. respected.


Training programs at 503B readiness facilities should include training on regulations and standards, such as cGMP and USP , in addition to specific job training in aseptic technique and dressing, among others. Various methods, such as skills assessments and written exams, are used to ensure that staff are qualified to perform their duties.


Validation is the collection and evaluation of data that establishes scientific evidence that a desired result with predetermined criteria will be achieved every time. Process validation makes a significant contribution to guaranteeing the quality of medicines. Every step of the drug preparation process is controlled so that the finished product meets its quality attributes and specifications. The validation of the test method ensures that the tests conform to USP standards. All product lots are thoroughly tested using validated methods before being put into service.

Equipment calibration and maintenance

A high degree of precision is required in the preparation of drugs. Equipment used in a 503B installation should be calibrated regularly to ensure accurate measurements. In addition, a preventive maintenance program ensures optimal operation of the equipment. Supplier qualification Suppliers of goods and services are checked and approved before purchasing their products. The qualification process is a way to ensure that the supplier can deliver components, packaging, materials, packaging and services of consistent quality in accordance with regulatory requirements.

Summary The 503B outsourcing facilities are the result of the DQSA. Establishing Section 503B enables health centers to obtain sterile pharmaceutical products manufactured with high levels of compliance and quality. Since 503B establishments operate on a larger scale compared to traditional 503A dispensing pharmacies, they are required to adhere to cGMP regulations. 503B establishments play a key role in healthcare due to their bulk production, strict quality standards and wide distribution. They bridge the gap between manufacturers of 503A pharmaceuticals and pharmacies, and ensure that the public has access to effective and safe drugs.

Sharyl Zaccaglino, MRS, is director of research quality
and compliance at the University of Rochester Medical Center in New York.

The references

1. Goldman TR. Regulation of compounding pharmacies. BusinessHealth. May 1, 2014. Accessed October 31, 20219. http://healthaffairs.org/healthpolicybriefs/brief_pdfs/healthpolicybrief_114.pdf

2. Multi-state epidemic of fungal meningitis and other infections – number of cases. October 30, 2015. Updated May 9, 2019. Accessed October 31, 2021. CDC. https://www.cdc.gov/hai/outbreaks/meningitis-map-large.html

3. Medicines Quality and Safety Act, HR 3204, 113th Cong, 1st Sess, §102 (2013).

4. Food and drugs. 21 CFR §210-§211 (1978).

5. Quality systems approach to current pharmaceutical regulations for good manufacturing. FDA. October 2006. Updated April 16, 2020. Accessed October 31, 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good -manufacturing -practice-regulation

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