With a purpose of writing and updating scientific information surrounding drug development, Chemistry, Manufacturing, and Controls is a key part of regulatory requirements when obtaining pharmaceutical approval from the FDA or EMA.
Sometimes, if a person is not properly trained or has not been part of pharmaceutical writing or submission teams in the past, they may miss critical aspects. A scientific person running a test might not fully understand the expectations of FDA guidelines or how to correlate analytical data with product quality, product design, or in-process control. This is where CMC writing becomes a crucial aspect in obtaining FDA approval.
Connecting Dots Between Scientist Expertise with Technical and Regulatory CMC Writing
Anything that you observe when you run an experiment, which is required for CMC, should be conducted according to guidelines provided by the FDA. While the FDA provides suggestions, adhering to the guidelines must be done meticulously. Failure to comply will lead to questions regarding your processes and decisions.
With a goal of achieving first-cycle approval of an NDA (New Drug Application), CMC must meet FDA goals- if it doesn’t, approval becomes questionable. Although statistically, first-cycle approval only happens 9% of the time, the expectation persists.
There are two sets of questions from the FDA:
- IR (Immediate Responses)
If you receive an IR, it means the application is still under review, and these are usually minor questions. If you do not provide quick, complete, or targeted responses, the IR can convert into a CR.
- CR (Complete Response)
A CR can take almost a year to address, delaying the approval process. This adds to the critical importance of CMC writing in the approval process.
High-Quality CMC Documentation for Regulatory Compliance
For any regulatory submission, compliance is crucial in the approval process. The goal of convincing the FDA to authorize the commercialization of the product should drive the entire CMC writing process.
Turning Scientific Documentation into Regulatory CMC Writing
At the foundation of CMC writing, you need to be able to scientifically write about what was done, what was not done, and how you reached your conclusions. To meet the FDA expectations, you must be specific. If your concepts are unclear, you might ask for a specification that your data does not support, leading to FDA denial and delaying the approval process.
A common challenge in aligning scientific documentation with regulatory compliance is a lack of regulatory training among pure scientists. Often untrained on the regulatory side, scientists can find it difficult to adjust their writing style to what’s required for regulatory submissions.
One of the best solutions to address this is challenge, is to train scientists on how to write in a way that seeks approval from reviewers who are not in front of us but will review the documents with specific expectations.
Bridging the Gap Between Industries
Another challenge that CMC writers face is that chemists from the analytical side often come from different industries. If they are not from the pharmaceutical industry, they may not understand the approval process of regulatory writing.
There are many differences between writing styles that can also lead to a resistance to change by scientists, questioning why they need to write in a certain way. The FDA prefers certain words and phrases that are commonly used, and both parties need to align to make the reviewer’s job easier and more favorable towards the FDA application.
How does CMC documentation impact the manufacturing and quality control aspects of pharmaceutical production?
The areas of focus for FDA approval are safety and efficacy, and reproducibility. If a product is approved today, it needs to remain identical for the next 20 years. To ensure this, they identify what are called ‘in-process controls.’ By consistently meeting these controls, we ensure that we also meet safety and efficacy requirements.
Product controls are constantly scrutinized and questioned to ensure they are sufficient. This led to the concept of Quality by Design (QBD), which means building quality into the product from the beginning. Unlike in the past when Quality Control was more common, now Quality Assurance (QA) is more prevalent, as it ensures that quality is inherent in the product design. QA reviews all data to ensure it meets FDA standards. Data integrity is another critical area for the FDA. During an audit, FDA investigators will thoroughly check our data handling processes.
When writing regulatory submissions, the writer must assure the reviewer of data quality and the effectiveness of the control strategy. Critical quality attributes and control strategies must be clearly articulated in the submission.
How do advancements in technology and data management systems influence the practice and quality of CMC writing in the pharmaceutical industry?
With a rapid advancement of technology sometimes guidelines, including those from the FDA, fail to keep up with these advancements. Consequently, CMC writing needs to simplify the scientific technicalities to ensure that reviewers, who may not be as familiar with modern technology, can understand it. It’s important to recognize that not all reviewers are lab scientists, and they may not be up to date with the latest technological developments.
As technology evolves, it is the responsibility of CMC writers to bridge this knowledge gap and ensure that this writing style is clear and comprehensible to all reviewers. It’s critical to remember the ultimate goal: obtaining FDA approval.
On the positive side, modern technology can help mitigate human error. For instance, providing machine-generated data printouts can instill greater confidence in reviewers, as they eliminate the possibility of human oversight or bias. In such cases, regulators may approve submissions more quickly, knowing that the data is directly from the machine and free from human intervention.
In conclusion, while technological advancements present challenges in regulatory writing, they also offer opportunities to streamline the approval process. By effectively communicating complex concepts and leveraging advanced technology, we can enhance the likelihood of obtaining faster approvals.
Why CMC Writing is a Trained Skill
All the above is why CMC writing is a specialized skill that combines scientific knowledge with regulatory requirements. It requires understanding USP and FDA guidelines, manufacturing processes, and analytical techniques. Training and a deep understanding of multiple facets are necessary to write effective submissions. This complexity makes CMC writing a critical and popular subject among companies.
Our team at LGM Pharma is ready to help you navigate the complexities of CMC writing – with expertise in partnering with you to assist you in receiving FDA approval and maintain compliance from concept to commercialization.