Data Governance and Data Integrity (DI)

Introduction:

Data governance and data integrity (DI) are important elements in ensuring the reliability of data and information obtained in the production and control of pharmaceutical products. The data and information should be complete as well as being attributable, legible, contemporaneous, original and accurate, commonly referred to as meeting “ALCOA” principles.

In recent years, the number of observations made regarding the integrity of data, documentation and record management practices during inspections of good manufacturing practice (GMP), good clinical practice (GCP) and good laboratory practice (GLP) has been increasing.

Possible causes for this may include

(i)                  too much reliance on human practices;

(ii)                 the use of computerized systems that are not appropriately managed and validated;

(iii)               failure to adequately review and manage original data and records.

What is Data Integrity?

data integrity refers to the completeness, consistency, and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA).

Line Clearance in Pharmaceuticals

 Line Clearance

What is Line Clearance :

Line clearance is a process that provides a high degree of confidence or assurance that the said line or area is free from any unwanted residue or leftover of previous processing before proceeding with the next process. Quality assurance has to provide Line clearance before the start of any activity whether it is batch to batch change over and Product to product change over.

 

Criteria of Batch to batch change over :

Change over from one batch to another batch of the same product and same Strength or increasing in strength provided the excipients are the same.

Cleaning between batches of the same product but in ascending or increasing strength.

Criteria of Product to Product change over :

1. Change over from one product to another product.
2. Change over from one product to the same product with descending or decreasing strength.
3. Change over between batches/products with different colors Flavour / Excipients.
4. Change over after post maintenance or when the next product is not known (as applicable).  
5. Continuously running one batch for a longer period of time.
6. Area or Equipment is kept ideal for more period of time.

Line clearance should be carried out at change over by Manufacturing, Packaging, Raw Material Store, Packing Material Store, etc independently for the stages where final dosage form & intermediates are formed, handled and processed.

Information Requests and Discipline Review Letters of US FDA

·         The Generic Drug User Fee Amendments of 2017 (GDUFA II) was signed into law on August 18, 2017 in order to facilitate timely access to high quality, affordable generic medicines.

 ·         As part of GDUFA II, FDA agreed to two program enhancements centered on improving communications during a review-cycle:

- Discipline Review Letters; and

- Information Requests.

 ·         The recently published draft guidance entitled Information Requests and Discipline Review Letters Under GDUFA, explains how the Agency intends to deploy these two program enhancements during the review of an original abbreviated new drug application (ANDA).

 

Discipline Review Letter (DRL)

Ø  Generally, a DRL will be issued from each discipline as it finishes its initial review of its portion of a received ANDA.

Ø  It will not represent a complete review of the entire submission and does not necessarily reflect input from all supervisory levels.

FDA approves first treatment for COVID-19

 

The U.S. Food and Drug Administration approved the antiviral drug Veklury (remdesivir) for use in adult and pediatric patients 12 years of age and older and weighing at least 40 kilograms (about 88 pounds) for the treatment of COVID-19 requiring hospitalization. Veklury should only be administered in a hospital or in a healthcare setting capable of providing acute care comparable to inpatient hospital care. Veklury is the first treatment for COVID-19 to receive FDA approval.

This approval does not include the entire population that had been authorized to use Veklury under an Emergency Use Authorization (EUA) originally issued on May 1, 2020. In order to ensure continued access to the pediatric population previously covered under the EUA, the FDA revised the EUA for Veklury to authorize the drug’s use for the treatment of suspected or laboratory confirmed COVID-19 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg. Clinical trials assessing the safety and efficacy of Veklury in this pediatric patient population are ongoing.

Different Types of Training in Pharmaceutical Industries

Training plays an important role in any industry and it gives a clear understanding about the roles and responsibilities of a person working in an organization.

There are different types of Training which are as follows:

(1)  Induction Training

(2)  On Job Training

(3)  Self Reading Training

(4)  Class Room Training

(5)  External Training

(6)  Incidental Training

(7)  Refresher Training

Induction Training:

Training given to the new joinee (Employee) at the time of joining the organization for awareness of organization and organization personnel is termed as Induction Training.

Whenever a new employee is joining the organization, on completion of joining procedure, Personnel – HRA shall give him / her first-hand information regarding the company’s profile, group activities, service benefits, service rules, administrative rules, disciplinary rules and personnel hygiene.

 Human Resource department shall also provide “Induction Manual” for awareness of the organization.

On completion of the reading of “Induction Manual”, Personnel – HRA shall take him / her for plant round to familiar with the plant as well as plant personnel.

On Job Training:

Training given to an employee at the workplace is termed as On Job Training.

Comparison of EU and US variation requirements

 Key points in regulatory management of variations

• Lifecycle management of pharmaceutical products varies between the EU and US in terms of different submission requirements and assessment timelines. However, similarities do exist in regional approaches to a general categorization of post-approval changes (variations) and in many cases also the principles of implementation.

• Post-approval variations in the EU and US can be administrative in nature, simple changes requiring minor review, or major changes that are often complex.

• Administrative: EU regulators go as far as to define “administrative” as a category in their classification guideline, whereas in other regions they fall into the lowest variation category and have significant crossover with minor variations, e.g. new addresses. Many agencies accept that these changes can be implemented without the need for approval. Prior approval of administrative changes is time-consuming for agencies and costly for industry. Additionally, in certain cases such as a marketing authorization holder (MAH) moving address, the change would actually need to take place prior to submission.

• Minor: Minor variations are generally considered to have either no impact on the quality of the product or have a very low chance of impact; and hence lower risk. Consequently, the level of agency review, and hence the time required is reduced. As regulatory frameworks have developed, agencies have introduced means to allow the most minor of variations to be implemented before review. For example, in the EU, when a Type IA variation is submitted the MAH must state which of a pre-defined list of conditions applies to its change, thereby reducing the amount of review required. With minor variations, many agencies have documentation requirements that are well-established and must be met before variations are submitted. This ensures that MAHs know what is expected before a submission and can prepare sufficient supporting data. This leads to faster review times as assessors have less need to request further data from applicants.

• Major: Where notable alterations to product registration are required, these are expected to have an impact on a product’s quality and efficacy and as such are tightly controlled, requiring in-depth assessment and review. The MAH must demonstrate that the product will retain the same level of quality and efficacy. Comparative data is a significant requirement for such changes and must reliably show the proposed changes do not impair product quality. Assessment times for such variations are often much longer, as agencies carefully review submissions and frequently make requests for additional data and answers to questions and concerns.

Table 1: Summary of variations and anticipated implementation dates in Europe and US.
Europe				US
Variation	Type	Anticipated implementation time	Guideline approval timeline	Type	Anticipated implementation time	Guideline approval timeline
Admin	Type IAIN	14 days before submission	N/A	AR	Up to 1 year before submission	N/A
	Type IA	Up to 1 year before submission	N/A
Minor	Type IB	Up to 3 months after submission*	30 days	CBE-0	On receipt of submission by FDA	N/A
				CBE-30	30 days after receipt of submission	6 months
Major	Type II	Up to 6 months after submission*	30 days	PAS	Up to 6 months after submission*	4 months
*The noted anticipated dates are based on experience with submitting variations to the relevant agencies and incorporate the time taken for validation, application assessment, applicant’s response to questions (clock stop) and assessment of responses.

European (EU) Variation Requirements

What is Variation:

Variation means any amendment to the terms of the decision granting the marketing authorization as well as any change to the summary of product characteristics and the documents forming the basis for an authorization to market a medicinal product.

European Commission has classified the variation type as type IA/IAIN, type IB and type II.

Type IA/IAIN (do and tell):

Changes that fall under this category are commonly referred to as “do and tell” variations because the applicant is required to implement the change and then notify the agency of the details.

This level of variation is reserved for administrative changes that are anticipated to have no impact on the quality, safety or efficacy of a product.

Variations that can be submitted as Type IA must be implemented and then the required submission made within 12 months of the implementation date.

 For changes that are categorized as Type IAIN the applicant must notify the agency within 14 days of implementation and for a single product multiples variation can be made at the same time, as long as all of them fall within the required submission deadline.

Type IB (tell, wait and do):

Minor variations that require assessment of supporting data and are anticipated to potentially have an impact on product quality, safety or efficacy are classified as Type IB and these are also referred to as “tell, wait and do” variations.

Type IB variations are minor variations, which are neither a type IA variation, a type II variation nor an extension.

The applicant must make the submission, including all required supporting data, and await agency approval before implementing the change.

The process follows a defined assessment period of 30 days, but with agency questions it can often take up to 03 months.