Updated: Sep 24
Let's review the following (worst case) scenario: You received a Warning Letter following an inspection from the U.S. Food and Drug Administration (FDA). Most likely, this letter will detail those observations that you and your team "failed" to address in your initial response to form FDA 483 and, in most cases, the letter will include suggestions that will help you to comply with Federal Regulations. One of these suggestions is to hire a cGMP consultant to assist your company in meeting cGMP requirements.
First and foremost, you should treat your Warning Letter with the highest importance. But why? you may wonder. Well, because this letter is coming directly from your most important customer, the FDA. A consultant will help your company to navigate through the web of federal regulations and clean your path to welcome current and prospective clients. Not being perfectly in compliance with these regulations pose a high risk to your organization to lose everything! It is then paramount that you and your employees stay always on top of this GMP “game” to help your company prosper.
If you decide to follow the FDA’s advice and hire a consultant, there are a few things that are crucial for you to consider and, thus, avoid wasting money and time. Remember, at first, the role of a consultant is no different than that of the FDA’s auditor; the main difference is that a consultant will help you and your employees to operate in full compliance with FDA’s regulations, whereas the FDA’s auditor will accumulate evidences to illustrate that your whole operation violates some cGMP regulations and will be conclusive by demonstrating that some of your products are not suitable for human or animal consumption.
Based on my experience (not only as GMP Consultant but also as a Director of Quality that had interacted with several Consultants), the following 9 points summarize the ideal characteristics of those consultants that will provide value to your company; this “value” can be measure in the following terms: presents solutions towards being GMP compliant, increases the quality in all production processes, fits perfectly within budget allowances, saves time, and eventually, helps to increase sales and revenue.
1. The consultant has a high degree in Science or Engineering, preferably a Ph.D., but could be a master’s degree as well.
This is of upmost importance because the best way to deal with problems in the production process is by using a scientific approach to find solutions and you want to have a consultant that is highly, on-hand, trained in the application of this method.
A “scientific approach” is nothing less than the application of the Scientific Method which consist of:
Make observations, i.e., it is uncertain that the raw material “Purified Water” used during the manufacturing of product X is safe for human or animal consumption.
Generate questions derived from previous observations, i.e., Is it possible to guarantee the safety of raw material “Purified Water” in my facility so it can be used in the manufacturing of all products that will be consumed by humans or animals?
Formulate hypotheses, i.e., the safety for human or animal consumption of products that contain the raw material “Purified Water” can be guaranteed if raw material “Purified Water” always complies with the following testing parameters: it's a clear, colorless and odorless liquid with low levels of bacterial and yeast and mold activity (< 1000 CFU/g) and absence of specific pathogens (E.coli, Salmonella, Staphylococcus aureus, Pseudomonas aeruginosa, etc.), with neutral pH, and total dissolved solids of no-more-than 5 ppm.
Develop testable predictions, i.e., if my hypothesis is correct, then, every time raw material “Purified Water” is tested the following results should be expected: a clear, colorless and odorless liquid with low levels of bacterial and yeast and mold activity (< 1000 CFU/g) and absence of specific pathogens (E.coli, Salmonella, Staphylococcus aureus, Pseudomonas aeruginosa, etc.), with neutral pH, and total dissolved solids of no-more-than 5 ppm.
Design an experiment or experiments to gather data to test predictions, i.e., create a Validation protocol to evaluate the quality or purity of raw material “Purified Water”. The testing parameters could be those delineated in the hypothesis and the data should be gathered during a per-defined period.
Analysis of results and conclusions, i.e., repeated experiments such as the one presented here will require a statistical analysis of the data. The results will help to decide the next set of actions to take. For example:
-- Scenario I: Every time raw material “Purified Water” was tested the following results were obtained: a clear, colorless and odorless liquid with low levels of bacterial and yeast and mold activity (< 1000 CFU/g) and absence of specific pathogens (E.coli, Salmonella, Staphylococcus aureus, Pseudomonas aeruginosa, etc.), with neutral pH, and total dissolved solids of no-more-than 5 ppm.
In this case we can conclude that raw material “Purified Water” is safe to be used in the manufacturing of products that will be consumed by humans or animals.
I will also propose to repeat the experiment every 6 months for the following 2 years. This will guarantee Replication of the experiment, another component of the Scientific Method; the expectation is that, under the same conditions, the experiment should produce the same results every time.
-- Scenario II: Every time raw material “Purified Water” was tested one or more parameters were outside the specifications boundaries.
This may suggest the need for an equipment upgrade before repeating the experiment.
The application of the Scientific Method is recommended by the FDA for the following: CAPA investigations, Validation of Processes (cleaning, blending, packaging, stability studies), Performance Qualifications, Verification, Clinical Studies, and introduction of new analytical methods in the laboratory, among others.
Whenever you are in doubt of the credentials presented to you by a potential candidate, if those credentials are from an U.S.A.'s accredited university or college, you can contact the Graduate School of such institution and ask for your candidate's transcripts. It won't cost you more than $5.00 dollars!
2. Knowledgeable of how the production process flow and what are those critical quality control points along this process.
The ideal consultant, especially for cGMP consultants, is that one that can easily identify those points, along the whole production flow, that are critical for control by Quality Assurance (QA) or Quality Control (QC) specialists. The whole production flow covers EVERYTHING from receiving raw materials to shipping off finished products.
3. Demonstrate resourcefulness.
It is more than OK not to know everything regarding GMP regulations and its details, it’s a fact; however, your ideal consultant should be able to first, recognize those areas where he/she lacks expertise but more importantly, he/she should be able to retrieve the missing information from a given number of sources. These sources could be literature, online resources, colleagues, collaborators, etc.
The same is applicable with deadlines. In this case your ideal consultant will have the knowledge but not the time to finish a task, then he/she should identify, and maybe subcontract, those collaborators that can help him/her finish the task within deadline’s boundaries.
In the case that you decide to hire more than one team of consultants, whether because budget deficit or abundance, or because you believe that having your company flooded with consultants will speed up the process (in most cases this situation creates more problems than solutions), then you should designate one consultant to oversee all consulting activities.
4. Should bring with him/her solutions, training and implementation plans.
The role of a consultant is to bring solutions to your problems; in most cases these solutions will disrupt the comfort in which your employees were used to operate, which converts the consultant in the person responsible to train your personnel and immediately oversee the implementation of the changes. This overseeing operation should last for a certain period to quickly correct potential errors.
What you don’t want is a consultant that will sit in a corner playing the role of an FDA’s auditor and constantly disrupting your normal operations. Such disruptions could be done by assigning several tasks to your company's key players; tasks that should be completed by the consultant instead.
5. Should demonstrate empathy.
After the initial protocols are completed, that is signing non-disclosure and confidentiality agreements between the parts (you and your consultant) and business protocols’ approvals, your ideal consultant should become part of the company; he/she should feel that sense of ownership and provide proper advise to you and your team on the best way to solve the problems at hand within the allotted time and must avoid at all cost non-constructive critics that could jeopardize the well-being of your company.
6. Should be able to blend well within your company’s rules and code of conduct.
7. Should be respectful with all your employees.
8. Should deliver reports that not only document the remedial period but also how the implemented changes have improved your organization.
Documentation is a key element to be GMP compliant. You may manufacture the best pain relief OTC cream in the World but if you fail to document the whole manufacturing process then you may face a recall that may cost you, at least, $600,000 dollars; on the other hand, you may manufacture the worst product in the World but have in place good documentation practices that back up your manufacturing process then, the likelihood that you will face a recall for that product, manufacturing wise, will be very small.
You should then expect your expert or consultant to lead by example.
For finished pharmaceutical products for instance, the Code of Federal Regulations (CFR) title 21 part 211.34 requires your company to maintain records of any consultants and the type of service they provide. Such records include the name, address, and qualifications of the expert.
9. Fair Compensation.
The minimum a consultant will ask for his/her services is $2,500.00 per week; the maximum is $300.00 per hour.
Bear in mind that you already have some sort of Quality System in place and your employees should have the qualifications and expertise to cover all the functions that your consultant will oversee. This means that the bulk work of a consultant shouldn’t last more than 6 months. You can, of course, continue using his/her services for as long as you want.
By fair compensation I mean a negotiation that will be beneficial for both, the company and the consultant. Negotiations are always possible, and your potential consultant is probably willing to work with you in a fair manner. Don’t forget that these consultants are, most of the time, not locals and that being away from home requires sacrifices.
Note: The SAR Group’s consultants are American citizens and can provide consulting services anywhere in the World.