Electronic Document Management System [EDMS]

Like procedures, protocols, methods, and specifications, documents provide instructions to perform tasks and make decisions safely, effectively, compliantly, and consistently. Records such as batch manufacturing records, cleaning logs and laboratory data sheets and notebooks provide evidence that actions were taken and decisions were made in keeping with procedures and GMP expectations. Reports are yet another type of documentation that provide specific information on investigation and aspects of product development in a formal, standardized way. Reports may include data summaries, findings, actions to be taken etc. Each document, records, and reports must be uniquely identified and included all GMP requirements.

Data Integrity (Part-III) (Some Major Observations)

Observation 1

Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards

The firm inspected lacked accurate raw laboratory data records for batches of API that were shipped. The inspection revealed that batch samples were retested until acceptable results were obtained. In addition, Quality Control (QC) laboratory failed to include complete data on QC testing sheets. Failing or otherwise atypical results were not included in the official laboratory control records, not reported, and not investigated.

Data Integrity Part-II (Laboratory)

Most companies have experienced being audited and, where necessary, “defending” the work carried out in their analytical laboratories during audits. Historically, laboratories have tended to provide information about the validation of their methods and procedures, the qualification and suitability of their analytical equipment, and information about training of their laboratory staff as justification for the validity of the analytical results.

Data Integrity -Part-I

The basic rules in any good manufacturing practice (GMP) regulations specify that the pharmaceutical manufacturer must maintain proper documentation and records.

Documentation helps to build up a detailed picture of what a manufacturing function has done in the past and what it is doing now and, thus, it provides a basis for planning what it is going to do in the future. Regulatory inspectors, during their inspections of manufacturing sites, often spend much time examining a company’s documents and records.

Data may be generated by

(i)                a paper-based record of a manual observation, or

(ii)              in terms of equipment, a spectrum of simple machines through to complex highly configurable computerized systems. The inherent risks to data integrity may differ depending upon the degree to which data (or the system generating or using the data) can be configured, and therefore potentially manipulated

Systems should be designed in a way that encourages compliance with the principles of data integrity.

Management of Corrective and Preventive Action (CA-PA)

The concept of Corrective and Preventive Action (CAPA) has doesn’t specifically appear in the older version of Good Manufacturing Practices. CAPA seems to have become popular in the pharmaceutical industry because of its use with medical devices.[ISO 13495:2003 and the FDA’s 1996 Quality System Regulation (QSR) for medical devices, include CAPA. This requirement for medical devices has been extended to the pharmaceutical industry as an expectation by US inspectors.

There are number of points that could trigger CAPA. For example, an investigation, a quality audit, an inspection by national authority, or a complaint. The system should be flexible enough to accommodate these different inputs.

Discussion for establishment of risk based approach on airflow visualization in cleanrooms

Smoke study or air flow visualization is the important factor in clean room qualification.
My query to some experts were as following

1. What will be the requalification frequency for Smoke study?
2. If there is no significant changes in the clean room design is it require to do periodic evaluation of smoke study?
3. Any Guidance available for video shooting?

I have received the following comments from  various experts (shared for public interest)  

Popular methods of Risk Assessment (Part-II)

Fault tree analysis

The fault tree analysis (FTA) was first introduced by Bell Laboratories and is one of the most widely used methods in system reliability, maintainability and safety analysis. It is a deductive procedure used to determine the various combinations of hardware and software failures and human errors that could cause undesired events (referred to as top events) at the system level.

The deductive analysis begins with a general conclusion, then attempts to determine the specific causes of the conclusion by constructing a logic diagram called a fault tree. This is also known as taking a top-down approach.

The main purpose of the fault tree analysis is to help identify potential causes of system failures before the failures actually occur. It can also be used to evaluate the probability of the top event using analytical or statistical methods. These calculations involve system quantitative reliability and maintainability information, such as failure probability, failure rate and repair rate. After completing an FTA, one can focus the efforts on improving system safety and reliability.

Popular methods of Risk Assessment (Part I)

Failure Mode Effects Analysis (FMEA)

Failure modes and effects analysis (FMEA) is a step-by-step approach for identifying all possible failures in a design, a manufacturing or assembly process, or a product or service.

“Failure modes” means the ways, or modes, in which something might fail. 

Failures are any errors or defects, especially ones that affect the customer, and can be potential or actual.

“Effects analysis” refers to studying the consequences of those failures.

Failures are prioritized according to how serious their consequences are, how frequently they occur and how easily they can be detected. The purpose of the FMEA is to take actions to eliminate or reduce failures, starting with the highest-priority ones.

Label Control

Overview

 

Controlling the storage and issuing of labels and labeling helps prevent mix-ups. Technology, such as bar-codes and vision systems, has reduced the number of   label - related recalls, but controlling label storage and issuance is still very important.

Regulatory expectation and guidance on Pharmaceutical market complaints

On way to manufacturing process end number of steps, tests, check, audits and evaluation is there combined with other quality system elements such as qualification validation and many more. All these impart confidence that the system or process is functioning as intended and assurance of safety, identity strength and quality. The last hurdle is that the product must successfully marketed: to the consumer or healthcare provider.

Still consumer complaints are unavoidable circumstances. It may range from “don’t smell right” to “insect parts are there inside the bottle during packaging” and the list can continue for pages and pages.

Complaints are generally thought of as communications concerning a real or perceived defect in the product or that the product fails to meet the expectations of the consumer. US FDA defines as “all scientific and data gathering activities relating to the detection, assessment, and understanding of adverse events”.

Where should airflow velocity measurements be taken, with respect to a filling line or other aseptic processing areas?

 

Recommendation

Airflow velocity measurements should be taken at locations where meaningful and reproducible results can be obtained. This typically at a distance of 15-30 cm from the filter face.

Rationale for Recommendation

The primary reason for airflow velocity measurements in unidirectional airflow areas (e.g, area where products , product contact packaging components, and product contact surfaces are exposed) is to ensure adequate airflow to protect the materials from external airborne contamination and to verify continued compliance with qualified conditions. The adequacy of the environment can be determined, in part, from airflow velocity and air flow pattern studies, and from particulate matter monitoring (at the working position).

Accurate measurements can be taken ad changes over the detected when air flow velocity are evaluated at a predetermined distance from filter surface, which is sufficiently close to the filter surface to be reproducible to detect changes in the performance of the filter.

The airflow velocity depends on the design of the filling line, room design, and air-handling system. Once velocity is determined, it is important to ensure that the velocity stays within the specific parameters. Routine air velocity measurements should be taken at the same locations used during the initial airflow studies to ensure consistency.

Application of near infrared spectroscopy to the analysis and fast quality assessment

NIRS combined with appropriate mathematical models and pattern recognition techniques allows analysis of a wide variety of sample types rapidly. Second, NIRS is a non-destructive technique which avoids complex sample preparation by chemical or physical processes. In fact, both solid and liquid samples in different types of packaging stored under different conditions can all be tested without complex pretreatment because of the better penetrability of fiber optics used in NIRS. Third, it provides acceptable accuracy in both qualitative and quantitative analysis to meet the requirements of QC and preliminary screening

When the FDA Inspector visits your firm, What are the Chances of a Really Bad Outcome?

It’s generally nerve-wracking when the US Food and Drug Administration (FDA) shows up at your door for an inspection. Even if you’re confident that everything is in good shape around every corner.

To ensure compliance with regulations, the FDA conducts inspections of all registered establishments. 

Once the inspection is closed out, it is categorized in one of three ways based on the objectionable conditions noted (if any):

NAI - No Action Indicated

VAI - Voluntary Action Indicated

OAI - Official Action Indicated

Interview Questions for Pharmaceutical industry related jobs (QA,QC,Production,RA,f&d) for B.pharma /M.pharma (Part 8)

Requested By: for KVR Sudhir
Organization: Pharmaceuticals
Category : Parenterals

Questions

A.     VIAL WASHING  MACHINE QUESTIONS

1. What is purpose of vial washing machine?

Objective: Cleaning of Vial externally and internally to reduce the bio-burden.

Note:  It is used as a primary packing material.

HVAC Control and Monitoring System Validation

The control and monitoring systems are considered the core of the environmental control system. The final performance of the environmental control system can be evaluated only after these have been validated.

PQ protocols covering this system, in general, include the performance challenges for the all the components of the environmental control system described in the foregoing. The system is challenged by simulating the process or at the time the aseptic processes qualification

or media fills are performed.

The validation protocols follow the same format structure outlined before for the architectural components.The following section provides a generic checklist approach used for the HVAC controls and monitoring systems validation. As indicated earlier, the HVAC systems could be either manually, electric, pneumatic, or electronically controlled, operated or monitored. Computer- or microprocessor- controlled equipment is subject to the software and hardware validation procedures that apply to computerized systems.

Major USFDA warning Letters observation from 2000

The United States Food and Drug Administration (FDA) defines a Warning Letter as

"...a correspondence that notifies regulated industry about violations that FDA has documented during its inspections or investigations. Typically, a Warning Letter notifies a responsible individual or firm that the Agency considers one or more products, practices, processes, or other activities to be in violation of the Federal Food, Drug, and Cosmetic Act (the Act), its implementing regulations and other federal statutes. Warning Letters should only be issued for violations of regulatory significance, i.e., those that may actually lead to an enforcement action if the documented violations are not promptly and adequately corrected. A Warning Letter is one of the Agency’s principal means of achieving prompt voluntary compliance with the Act.