Consulting Quality

FDA warning letters often suggest that the pharmaceutical manufacturer receiving the letter hire a quality consultant to assist the company in fixing quality control problems at their facilities. What role can a quality consultant play in helping biopharmaceutical companies stay compliant? What measures should be taken to ensure the best match for the situation?

Pharmaceutical Technology spoke with experienced consultants—Aloka Srinivasan, principal and managing partner at RAAHA; Chris Moreton, PhD, partner with FinnBrit Consulting; Philip E. M. Crooker, J.D., vice president, Technical Regulatory & Access, Parexel; and Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates (RCA)—to gain insight on these questions.

Why hire a quality consultant?

PharmTech: What are the reasons a pharmaceutical manufacturer (sponsor or contractor) might hire a quality consultant?

Srinivasan (RAAHA): The reason for a pharmaceutical manufacturer or sponsor to hire a quality consultant may vary based on the size of the company, availability of in-house expertise, and the nature of the projects. In many cases, small companies prefer to use the service of quality consultants for their projects rather than hiring permanent staff. This gives them the flexibility of getting appropriate expertise based on the nature of the work, and can also be a better option, financially. However, mid-sized or bigger companies may also hire quality consultants when they are venturing into something new and the in-house expertise needs augmentation.

While in most cases the CMO/CDMO [contract manufacturing organization/contract development and manufacturing organization] may be hiring a quality consultant for the same reasons as the sponsor, there may be some areas where the CMO/CDMO’s reasons may be different. The CMO/CDMO may hire a quality consultant for a purpose which may be more specific.

Example, for a complex product, the CMO/CDMO may hire a consultant with a specific analytical skill related to a product that they are developing for better understanding the quality issues specific to the product or process. Overall, quality consultants are considered valuable by sponsor companies as well as CMO/CDMOs.

Moreton (FinnBrit Consulting): There are several reasons for sponsors to hire a quality consultant, but it all boils down to cost and head count. Many small biotechs do not have enough business to employ a full-time quality specialist and a consultant fits their model. For CDMOs, the reasons may be different. They may want to have someone review their quality systems and operations to point out any gaps ahead of a regulatory inspection. Or they may be moving into a new phase (e.g., from pre-clinical to clinical/commercial and need advice).

Crooker (Parexel): Start-ups and small companies may not have the resources to hire quality staff in-house and thus may seek experienced quality consultants to fulfill CGMP [current good manufacturing practice] regulations, which require a fit-for-purpose quality system and appropriate QA [quality assurance] functions at the manufacturer. Companies may need immediate access to deep skills in a highly specialized area (e.g., forensic investigation skills to examine data generated, collected, and reported during various stages of drug development, manufacturing, and regulatory submissions). Mock assessments and ‘pressure testing’ in between regular testing of quality systems helps manufacturers identify and mitigate gaps in advance of pre-approval inspections, post-approval audits, routine surveillance, and for-cause inspections after a product has been approved for marketing.

Health authorities may request, or require, the hiring of quality consultants to review a company’s quality systems and its remediation plans prior to or following enforcement action against a company, especially for serious or pervasive violations (e.g., when they enter into consent decrees or corporate integrity agreements with the US Department of Justice). Companies may seek quality consultants who were former regulators—such as field investigators, application reviewers, or compliance inspectors—to provide real-world insights about how a health authority would likely examine or respond to an issue.

Schniepp (RCA): There are several reasons a pharmaceutical company might hire a quality consultant. In many cases the company may need expertise regarding special subjects that company personnel may not possess. For instance, a company may wish to upgrade their water system. They may wish to hire an outside consultant with significant experience in designing and installing water systems. A small start-up or virtual company may wish to hire consultants to help establish their quality systems and standard operating procedures because of the small staff that often plays multiple roles in the organization.

Companies might also hire consultants to help them work through significant compliance issues as a result of regulatory inspections. In some cases, the hiring of a consultant is in direct response to a warning letter recommending the firm hire outside expertise to assist the company in reestablishing compliant behavior and robust processes. The reasons for hiring consultants, whether you are a sponsor company or a CMO/CDMO, are consistent.

PharmTech: What are the benefits or hiring a quality consultant? Are there any negatives to hiring a consultant?

Moreton (FinnBrit Consulting): Basically the advantages are head count and cost. The negatives are that the consultant may not be immediately available. In addition, a consultant may not be so intimately familiar with the activities of their client, and this can lead to misunderstandings.

Srinivasan (RAAHA): There are several benefits to sponsor companies as well as CMO/CDMOs of hiring a quality consultant. The major benefit is that a sponsor or CMO/CDMO may be able to customize their engagement of a quality consultant to meet their specific needs. Several quality consultants with diverse expertise can be engaged at the same time to work on different projects. As the involvement of the consultants in most cases is for the duration of the projects, the process is advantage from the perspective of human resources management, as hiring several permanent employees for the same purpose may come with its own challenges. Also, based on the contracts between the sponsors/CMOs/CDMOs and the consultants, the timeliness of the deliverables can be assured, which in turn can help keep the projects in time and within budget.

There are a few downsides of depending fully on quality consultant. Hiring the right person for the right job can be challenging based on just the review of a CV or a brief interview of a consultant. Finding a good quality consultant can be difficult. Also, an external consultant, who is hired for a limited time may not feel the same ownership of a project that a permanent employee does. There may also be lack of quality in the deliverables, or lack of chemistry between the permanent staff and the consultant, which could cause unnecessary hindrance to the progress of the project. Finally, if the agreement with a consultant does not cover all aspects of the engagement, a consultant’s decision to discontinue with a project midway can inconvenience the company/CMO/CDMO significantly.

Crooker (Parexel): A specific skill or situation can be aligned with the consultant’s background and for the desired length of time needed to address the issue(s). Consultants who have experience in both private sector and a health authority confer a broader perspective and view manufacturing issues through a multi-faceted lens. A wide array of prior client engagements increases the consultant’s vantage point of possible gaps and thus their effectiveness in finding and remediating gaps in quality systems before they are identified by health authorities.

Schniepp (RCA): The quality consultant typically has a number of years of experience and has seen a variety of issues that add depth to their understanding of issues. They also bring a third-party perspective, which allows them to view the organization with a fresh perspective and offer solutions that might be more effective in addressing issues facing the hiring company. Consultants usually have a broad base of experience and knowledge, and this allows them to view operations with a unique perspective. There are few negative issues when hiring a consultant provided the hiring company spends the time to review the qualifications of and interview the consultant to make sure they have the appropriate background, expertise, and demeanor for the project they are being consulted on.

PharmTech: What specific services can a quality consultant provide?

Moreton (FinnBrit Consulting): It depends; anything from advice on quality management systems and documentation to release of a batch of product. They can also advise on or undertake internal audits. Should it happen, they can also help in the remediation of FDA findings (483s and warning letters through to consent decrees)

Schniepp (RCA): Quality consultants can provide a number of specific services to a company. They can assist in establishing a robust quality system, responding to regulatory inspections, performing supplier audits, helping implement new regulatory requirements, and advising on complex and challenging investigations.

Srinivasan (RAAHA): They may help with development of quality assurance-related complex products, support with communications with regulatory authorities (483 responses, warning letter-related communications), train the staff related to various aspects of quality control, review regulatory materials, perform gap evaluations in the process, data acquisition and perform due diligence in mergers and acquisitions, perform audits, [and provide] support with solving numerous compliance related problems. Some of the quality consultants may have specific expertise in specific dosage forms [and/or] devices, which may be of great support to the sponsors/CMOs/CDMOs.

What to consider when hiring a consultant

PharmTech: What are the steps for hiring a quality consultant?

Crooker (Parexel): Companies identify quality consultants by surveying the marketplace (via websites, social media, online references), acting on recommendations, and using companies they’ve successfully engaged in the past. Once identified, consultants may be asked to submit a proposal to the company.

Based on the combination of the firm’s review of the consultant’s credentials and the response to the proposal, the firm can decide to move forward in the process and award the work to the consultant and reach a contractual agreement, negotiate further with the consultant or the consulting company, or continue their search without reaching an agreement. Manufacturers may have internal processes hosted by numerous functions—such as quality, technical operations, supply chain, and human resources—that they use to evaluate and select service providers.

Srinivasan (RAAHA): There is no specific rule for hiring a consultant. There are several organizations that have pools of consultants with diverse skills and may be able to provide a company/sponsor/CMO/CDMO with a list of qualified consultants who have experience in the specific area. However, one should never hire a consultant based on just the qualification. It is imperative that the hiring manager, and possibly the other members of the department who are expected to work closely with the consultant, interview the consultant before hiring.

Certifications in specific areas may be helpful. There are also some certification programs like the [Regulatory Affairs Professionals Society] RAPs Certification. Again, the value added by these certifications are questionable. There may be excellent consultants who do not have any certification. More than certification, the qualification and interpersonal skills of the consultant and references should be the prerogatives in the selection process.

It is important for a hiring manager to select a few consultants who have the required skills and come highly recommended. The hiring manager should personally interview them to assess if the personality of the consultant aligns with that of the staff and the general culture of the company and select the best match.

Schniepp (RCA): The first step for hiring a consultant is to write a scope of work for the job you are wanting the consultant’s help with. After that is finished, you can search for consultants/consulting firms that specialize in the area you are seeking expertise. It is important to screen the consultants to make sure you obtain the best consultant.

Some quality consultants may have certification, especially those consultants specializing in auditing. What’s more important than certification is experience and active involvement in the industry. Many consultants maintain their credentials and stay up to date by being members of trade organizations or writing books and articles. This experience is sometimes more important than a certification.

Moreton (FinnBrit Consulting): There is no set process. The prospective client should undertake a thorough due diligence and ask for references or cerifications such as [American Society for Quality] ASQ certification. However, there is no obligatory certification in the United States.

PharmTech: How does a quality consultant work with a company’s inhouse quality departments?

Srinivasan (RAAHA): There may be various ways that a quality consultant works with a company’s in-house quality departments. The simplest one is ad hoc consulting. The consultant may be contracted based on need by the members of the specific department. Alternatively, a quality consultant is embedded in the department for an extended period. In this case, the consultant will need to undergo training based on the company SOPs [standard operating procedures] specific to the service he/she is providing and made aware of the working norms of the company. It is the responsibility of the hiring manager to make the consultant aware of his/her responsibilities and the company staff aware of the boundaries related to interaction with the quality consultants.

Schniepp (RCA): I think it is important to introduce the concept of a contract worker versus a quality consultant. Companies could have both of these consultant types working for them, but the roles and interactions will be different. Contract worker consultants are usually filling in and performing a specific job. They would interact with management just as a full time employee would interact. A quality consultant who’s role is to advise, guide, and teach should interact with management in a mentoring role. They should give management choices and options for achieving the assignment. These options and choices should be ranked from least risky to most risky with an assessment explaining why the options are ranked as they are. Their recommendations should also be supported by the regulations. The consultant should also provide implementation recommendations and potential improvements to be introduced over time to ensure continuous improvement.

Moreton (FinnBrit Consulting): It depends on the nature of the consulting. There can be resentment and denial on the part of the client staff and senior management needs to explain the reasons for engaging a consultant, and obtain staff buy-in.

Crooker (Parexel): Collaborations vary according to the nature of the concern, timing, severity of the issue, and the company’s preferred style or approach. The consultant could be embedded within the firm’s QA unit as a dedicated resource, as a temporary employee, or as a ‘person in the plant.’ The consultant could function semi-independently, simulating the role of health authority personnel conducting or evaluating an inspection where the involvement with the firm’s QA unit is at arm’s length. And then there are situations that synthesize elements from both approaches, where the consultant collaborates with the firm’s QA unit to review the results from gap analyses, assists the firm in implementing CAPA and strategic changes, or participates in responding to health authority inspection results.

PharmTech: How long should a quality consultant be retained? Should the consultant be a embedded service or only hired to help investigate and correct specific quality issues/problems (such as an FDA warning letter)?

Schniepp (RCA): There really is no set timeline for how long a consultant should be retained. It will depend on the scope of the project and the time the company sets for completion. What is important is for management to make sure that the consultant remains independent and provides the third-party advice they were hired to provide. Consultants must guard against getting too comfortable with their client, so they can retain their independence and unbiased view of the operations they are working to improve.

I think that consultants can be either embedded or assigned to specific projects. There is a need for both of these service categories. The best way to manage the consultants in either role is to make sure the scope of the work you want them to perform is clearly defined to avoid scope creep and that they adhere to the specified project timeline unless there is an acceptable and understandable reason for a delay.

Srinivasan (RAAHA): The length of time for which a consultant is retained depends on the nature of the work and the company. A consultant may work for an extended amount of time with a company, where they provide advice when needed. There are instances where a consultant has been involved with a company for years, advising the staff, when needed, on various quality issues. Alternatively, when resolution of quality issues is sought (FDA 483s, warning letters), the consultant may be retained till the problems are resolved. In some cases, quality consultants may be proactively hired to perform gap analysis of various quality system as well as evaluation of data integrity. However, an important part of hiring a consultant is to have a clear view of how long the service is required. If a consultant has been in a site for more than a year and it appears that he/she will need to be there for more time, it is possible that a permanent employee is needed for the role.

Moreton (FinnBrit Consulting): I know of quality consultants who were hired over several years at the same company, especially in the early days of start-ups as they transitioned into clinical trials, etc. However, most quality consultants are engaged for short periods, for fixed projects.

PharmTech: Should a pharmaceutical manufacturer rely only on a quality consultant or still retain their own inhouse quality control and quality assurance departments?

Crooker (Parexel): From the perspective of the health authorities, it is expected that companies—regardless of their size or the type of organization—will have a fit-for-purpose QA function to meet CGMP regulations. The number and type of in-house quality personnel will vary across companies, but product owners and contract manufacturers cannot fully delegate CGMP compliance duties. They are responsible for the quality of the products they own and their manufacture. Thus, it is highly recommended that a firm—whether a product owner or contract manufacturer—hire the necessary in-house personnel who will own responsibility for the firm’s quality operations and decisions. These personnel can be supported by consultants, but it enhances the companies’ ability to comply with the CGMP regulations if they have established QA functions and processes in place as part of their organizations.

Schniepp (RCA): From my perspective, it is better to retain an in-house quality control/quality assurance department because they will have day-to-day familiarity and knowledge of processes which can help in deviations and investigations. This knowledge is also valuable during audits because they can explain the operations to the auditor and potentially clear up any misunderstandings before they become observations. I think it is also important for companies to have a network of consultants they also rely on to help out when things start to go awry. I think the most successful organizations rely on their internal staffs and their trusted consultants to set the best culture for the company while maintaining compliance to the regulations.

Moreton (FinnBrit Consulting): If [the company is] undertaking routine clinical and/or commercial manufacture in-house, they should have their own full-time quality control and quality assurance groups. They can bring in consultants as advisors and for special projects.

Srinivasan (RAAHA): It is preferable that a pharmaceutical manufacturer has an in-house staff in all departments, especially in the quality control and quality assurance departments, who are supported by consultants as and when needed. The reason for this is the importance of ownership and responsibility related to quality of products and process. It is well known that quality-related matters can be critical for a pharmaceutical company, and having at least a limited number of internal staff in charge, supported by quality consultants, is a better option. In case it is necessary to assign the responsibility of quality control and quality assurance entirely to a consultant, selection of the consultant should be made judiciously to assure that he/she is responsible, qualified, and capable of understanding the seriousness of the assignment.

To conclude, a quality consultant can be an asset to pharmaceutical manufacturer/CMO/CDMO when appropriately engaged. However, the industry representatives should use good judgment in hiring the right person and work collaboratively with the consultant to assure the best results.

About the Author

Susan Haigney is managing editor at Pharmaceutical Technology.

Article Details

Pharmaceutical Technology
Supplement: Outsourcing Resources 2020
Volume 44
August 2020
Pages: s29–s33

Citation

When referring to this article, please cite it as S. Haigney, "Consulting Quality," Outsourcing Resources Supplement (August 2020).