It is known that the standards that regulate the manufacture of products are established in industries, to validate the quality of everything that is produced and delivered in their respective markets. For the pharmaceutical industry, RDC 301 entered into force in August 2019, which regulates Good Drug Manufacturing Practices. In fact, it is the replacement of an existing Collegiate Board Resolution that for more than a decade was not updated, rdc 17/2010.
The fact is that with the growth of the market beyond our borders and, with this, the need for Brazilian industries to export the medicines produced in the country, RDC 301/2019 validates the quality of pharmaceutical manufacturing processes, even preparing them for export and compliance with critical standards of international markets.
To get an idea of the potential of this scenario, in 2019, Brazil exported a total of US$1.18 billion in pharmaceuticalproducts. In the previous year (2018), Brazil was already considered the South American country responsible for 2.6% of the global pharmaceutical market, according to a survey by Statista.
Therefore, RDC 301 came into force contemplating more severe requirements related to the production of pharmaceutical products by Brazilian companies in this sector, even being applied to entrepreneurs involved in product manufacturing projects experimentally.
Get to know some Normative Instructions of RDC 301
RDC 301 has several Normative Instructions (INs) tied to it, in addition to important other RDCs, such as the new RDC 430/2020 good distribution practices. See here the list of Normative Instructions belonging to RDC 301:
|IN 35/2019||Good Manufacturing Practices complementary to sterile medicines.|
|IN 36/2019||Good Manufacturing Practices complementary to organic ingredients and medicines.|
|IN 37/2019||Good Manufacturing Practices complementary to radiopharmaceuticals.|
|IN 38/2019||Good Manufacturing Practices complementary to gases active substances and medicinal gases.|
|IN 39/2019||Good Manufacturing Practices complementary to herbal medicines.|
|IN 40/2019||Good Manufacturing Practices complementary to the sampling activities of raw materials and packaging materials used in the manufacture of medicines.|
|IN 41/2019||Good Manufacturing Practices complementary to liquid medicines, creams or ointments.|
|IN 42/2019||Good Manufacturing Practices complementary to pressurized aerosol medicinal products with treatment for inhalation.|
|IN 43/2019||Good Manufacturing Practices complementary to computerized systems used in the manufacture of medicines.|
|IN 44/2019||Good Manufacturing Practices complementary to ionizing radiation in the manufacture of medicines.|
|IN 45/2019||Good Manufacturing Practices complementary to experimental medicines.|
|IN 46/2019||Good Manufacturing Practices complementary to blood products.|
|IN 47/2019||Good Manufacturing Practices complementary to qualification and validation activities.|
|IN 48/2019||Good Manufacturing Practices complementary to reference and retention samples.|
Attention to risk management
One of these requirements is risk management with proactive and retrospective criticalanalysis throughout all phases of the life cycle of the produced drug. This should be considered from experimentation, technology transfer, commercial manufacturing to product discontinuation. Here it is essential that the analysis is based on scientific knowledge and experience with a focus on ensuring patient safety.
To do so, it is necessary to implement a Pharmaceutical Quality System (SQF), defined in the manufacturer’s Quality Management plan, including performance monitoring and continuous improvement of manufacturing processes. It is also necessary a strict quality control from the collection of samples, specifications and proper tests required, certifying the quality attested for the release, distribution and commercialization of the manufactured product.
Similarly, in the event of an occurrence, the manufacturer must have a well-prepared plan for the immediate withdrawal of products from the market, reducing risks to the population.
Important additional considerations
In addition, RDC 301/2019 also requires the continuous qualification of professionals working in pharmaceutical industry activities, especially regarding individual responsibilities and manufacturing processes. Even activities carried out by third-party companies should have a clear and well-defined scope, agreed between the parties and in accordance with the Good Practices of RDC 301/2019.
The cleaning and maintenance of machines in manufacturers’ facilities are also issues that must be addressed, as well as minimizing errors with each implementation of new projects involving equipment. For example, the accumulation of waste should be avoided to reduce any risks of contamination in the product manufacturing process.
Another point is the care of the storage site. Factors such as lighting, stock room temperature and even humidity should always be monitored to keep the quality of the drugs intact.
Important points of RDC 301
The following are some important points of RDC 301 for pharmaceutical industry product manufacturers:
- Periodic Product Review or Periodic Quality Review (PPR) of all authorized medicinal products (including exclusive export products) should be conducted to verify the consistency of the existing process, the adequacy of the specifications applied to both raw material and finished product, evidencing any trends and identifying improvements in products and processes.
- Training. Everyone involved in the drug manufacturing process should be aware of the principles of Good Manufacturing Practices that affect them and therefore receive initial and ongoing training, including hygiene instructions relevant to their needs.
- Designation of people. There should be no gaps or overlaps of unjustified liability with regard to personnel involved in the application of Good Manufacturing Practices. In addition, key positions should normally be occupied by full-time staff.
- Consultants. Consultants should have adequate instruction, experience and training so that they are able to provide guidance on the topic for which they have been selected.
- Qualification of suppliers. The selection, qualification, approval and maintenance of raw material suppliers, together with their purchasing and acceptance process, should be documented as part of the pharmaceutical quality system.
- Cleaning validation and toxicity study. Design and design should minimize the risk of errors and allow effective cleaning and maintenance to avoid cross-contamination, dust or dirt build-up or any damage to the quality of the products.In addition, a Quality Risk Management process, which includes toxicological and power assessment, should be used to assess and control the risks of cross-contamination presented by manufactured products.
- Analytical validation, cleaning, process and computerized system. The design and use of the installation/equipment, personnel and material flow, microbiological controls, physical-chemical characteristics of the active substance, process characteristics, cleaning processes and analytical capabilities related to the relative limits established from the evaluation of the products should also be considered.
- Program, monitoring and stability study. After marketing, the stability of the medicinal product should be monitored in accordance with a continuous and appropriate programme, which allows the detection of any stability issue associated with its formulation.
- Technical transfer of analytical method. Before the process of technical transfer of an analytical method is initiated, a fault analysis should be performed and documented to identify any need for further validation. The transfer of analytical methods from one laboratory to another should be properly described in a detailed protocol.
- Outsourced activities. Any outsourced activity, the scope of which is subject to GMP, must be adequately defined, agreed and controlled, to avoid misunderstandings that may result in a product or operation of unsatisfactory quality.
Keeping an eye on rdc reviews 301/2019
Annually, revisions of RDC 301/2019 may occur, so we recommend that manufacturers operating in the pharmaceutical industry always be aware of new production requirements.
We at Kivalita Consulting can help you by sharing the latest information on this topic, here on our blog. Subscribe to our Newsletter and receive information about the news of the pharmaceutical market.
If you would like to learn more about our audit services for quality validation of pharmaceutical production processes and compliance with RDC 301/2019, talk to our experts!