Dr Md Anawar Hossain
- The good quality of active pharmaceutical ingredients (APIs) can ensure the manufacturing of the high quality, effective and safe essential drugs, while the use of low quality APIs can produce less effective and unsafe drugs.
- The price volatility of APIs can affect the small pharmaceutical companies.
- One potential way to address the above problems would be to broaden the WHO prequalification system and include APIs for drugs that are on the WHO model list for essential medicines.
Prequalification of Active Pharmaceutical Ingredients
Prequalification of active pharmaceutical ingredients (APIs) is an important step to ensure the production of good quality APIs. These products should be manufactured in compliance with WHO (World Health Organization) Good Manufacturing Practices (GMP). The pharmaceutical companies should use the prequalified APIs to manufacture their finished pharmaceutical product (FPP).
The API manufacturers must submit their API master file procedure (APIMF) to get their application approved for prequalification of an FPP (WHO, 2022). The APIMF includes the manufacturing details, quality controls procedure, accepted active ingredient specifications, and the assay and related substances test methods for assessment and any changes, before or after prequalification, is included in the updated APIMF version, which, therefore, clearly identify an API with a specific APIMF version. Active pharmaceutical ingredient manufacturers should apply to receive a WHO Confirmation of API Prequalification and obtain successful prequalification, before their APIs are included in the WHO List of Prequalified Active Pharmaceutical Ingredients (WHO, 2022).
API Manufacturer’s Site Inspection
The site of the API manufacturer should be inspected by WHO and verified whether it complies with WHO GMP requirements (WHO, 2022). The API manufacturing companies should apply along with a site master file (SMF) for each manufacturing site of each API and intermediate involved in the preparation of the API related to prequalification sought. An SMF contains the information about the production and/or quality control of pharmaceutical manufacturing operations conducted at a site, and any related integrated operations conducted at adjacent site or buildings.
Source, Quality and Price of Active Pharmaceutical Ingredients
The good quality of active pharmaceutical ingredients can ensure the manufacturing of the high quality, effective and safe essential drugs. The manufacturing cost of the final finished medicine product depends on the purchase price or manufacturing cost of APIs. In the developing countries, most of the pharmaceutical companies purchase APIs from other manufacturers. Only a limited number of large manufacturers of finished pharmaceutical products have their own API manufacturing capabilities in the developed countries, but none of them can make all required APIs in-house. The small manufacturers in developing countries face difficulties to source the global API market and ensure that they get a quality product at a fair price. Besides these, there is possibility that the greedy manufacturers or traders can control or monopolize parts of the API market for essential medicines with low commercial attractiveness. Given the limited sources of APIs, the manufacturers can increase the price of APIs to make more profit (Bumpas and Betsch, 2009).
One potential way to address this problem would be to broaden the WHO prequalification system and include APIs for drugs that are on the WHO model list for essential medicines.
Quality of APIs and Their Effect on Effectiveness of Medicine
The high quality of active pharmaceutical ingredients has a great effect on the effectiveness and safety of medicines. Active pharmaceutical ingredient is the central component of medicine. Sometimes, more than one API is used in one medicine. The quality requirements of an API help the manufacturer to determine the use of ingredients and the permissible limit of usage.
Properties and Purity of APIs
The active pharmaceutical ingredient has three main properties such as physical, chemical and biological properties, which can be used in the treatment of diseases. Active pharmaceutical ingredients may have chemical impurities. In addition, the impurities may come from the solvent used in mixing of ingredients. Therefore, the manufacturers should test the potency of the medicines. The physical properties of APIs, such as particle size/proportion and polymorphism are critical factors for suitability of an API for drug use, which control the flow properties of the API, rate of absorption and the bioavailability of the medicine. The particle size of the ingredient controls the solubility of the medicine in human body. The manufacturing process must ensure that the APIs are clean enough for use in non-sterile dosage formula, free from biological threat and toxins (Mankind Pharma, 2022).
References
Bumpas J, Betsch E, 2009. Exploratory study on active pharmaceutical ingredient manufacturing for essential medicines. Health, Nutrition and Population (HNP) discussion paper; World Bank, Washington, DC. © World Bank. https://openknowledge.worldbank.org/handle/10986/13682 License: CC BY 3.0 IGO.
Mankind Pharma, 2022. Quality factors for active pharmaceutical ingredients. Link: https://www.mankindpharma.com/blog/quality-factors-for-active-pharmaceutical-ingredients. Accessed on 13/06/2022.
WHO, 2022. Active Pharmaceutical Ingredients. Prequalification Procedures and Fees: FPPs, APIs & QCLs.
