Monday, June 29, 2009

Elements of Obama's healthcare reform plan

Obama expects to see a healthcare bill by end of 2009. The most important factor is to be discussed is increased insurance access for the under and uninsured.Reports from wasignton D. C suggest that a serious effort will be under way through out the summer to craft bill and get it to the President's desk for signature before end of the year.
I found a good report on these developments from Pharmavoice.
click on the link to read the full article

Voice of the Customer Executive Management

I found a new keyword ExecutiVOC™
ExecutiVOC™ is a process of executive management of VOC that reduces product development risk by providing oversight, direction and guidance at key points or milestones of the VOC process.. Through ExecutiVOC™, the process of executive oversight of VOC is demonstrated. ExecutiVOC™ is a process of executive management that reduces product development risk by providing oversight, direction and guidance at key points or milestones of the VOC process.

To know more about it attend the webinar by ComplianceOnline
Product Success during the Development Process through ExecutiVOC™

Friday, June 26, 2009

Acceptance Sampling as a tool

Statistical procedure used in quality control. Acceptance sampling involves testing a batch of data to determine if the proportion of units having a particular attribute exceeds a given percentage. The sampling plan involves three determinations: (1) batch size; (2) sample size; and (3) maximum number of defects that can be uncovered before rejection of the entire batch. This technique permits acceptance or rejection of a batch of merchandise or documents under precisely specified circumstances.

Acceptance sampling is a valuable tool often used (and misused) in the manufacturing sector. The most common methods employ standards so you can look up a sampling plan. The user has many choices, and needs to understand their impact on cost and risk. This seminar explains how to apply Z1.4 and c=0 plans.

To know more about it click on the link below
Understanding Attribute Acceptance Sampling including Z1.4 and c=0 Plans

Steam-In-Place (SIP) strategy

One of the most common methods for creating a sterile bioprocessing environment is the use of heat in the form of steam to eliminate unwanted organisms. Steam-In-Place (SIP) is a good sterilization method and involves sterilizing by means of steam the interior of pipes, vessels, process equipment, and associated fittings, without disassembly.
Steam-in-Place (SIP) can be a critical element in any startup and commissioning project. However, the full range of SIP strategies are not always thoroughly understood, and thus many manufacturers miss important elements of these techniques.
To know more about the application of SIP, about • Bioburden reduction• Saturated steam conditions: Temperature/pressure relationship• Autoclaves, vessels, filters and transfer lines• Empty- and full-vessel SIP• Proper use of Tempilstik®
Attend the webinar
Effective Steam-in-Place Strategies to Consider before Qualifying a Facility

How Green Is Your Plant?

While the automotive, chemical, cosmetic industries have made strides in reducing their carbon impact, the pharmaceutical and biopharmaceutical industries have lagged behind. It has been estimated that organizations can reduce their Carbon Footprints by as much as 20 per cent through the implementation of lean processes. By applying operational excellence techniques, a strategy can be developed to assist pharmaceutical manufacturing and supply chain operations to achieve more “Green Operations”. By adopting a focused practice to inventory wastewater, hazardous and solid waste streams, and energy consumption a facility’s carbon footprint can be determined. Efforts can them be focused on key waste generating areas such as gowning, facility cleaning, equipment cleaning and process operations. Not only will these efforts reduce the environmental impact of manufacturing operations, but they will ultimately reduce costs. Risk management and Quality-by-Design approaches will enable firms to better understand cleaning cycles, optimize them and reduce water, chemical, time and energy requirements. More efficient cleaning cycles result lower these resource demands and reduce the Carbon Footprint of these waste generating operations.Such strategies can help manufacturing achieve “Green Operations” in the face of mounting pressure for more environmentally friendly corporate citizenship drug manufacturing costs.

You can attaend this webinar to know how to develop a strategy for it
How Green Is Your Plant? – Determining the Carbon Footprint of Your Operations

Tuesday, June 16, 2009

Residual Solvent Analysis According to USP <467>

•“ Residual solvents in pharmaceuticals are defined as organic volatile chemicals that are used in the manufacture of drug substances and impurities or excipients, or in the preparation of drug products
•Residual solvents refers to the amount not removed during the purification of the product
•Residual solvents are one of the three main types of impurities in pharmaceutical articles (other two: organic and inorganic impurities)
•Residual solvents need to be controlled (ICH, USP, EP) and control is enforced (e.g., FDA)
USP Requirements

•All drug substances, excipients, and drug products (dosage forms) are subject to relevant control of residual solvents, even when no test is specified in the individual monograph
•Acceptable limits depend on solvent classification(toxicity, consistent with risk based approach)
•USP incorporates ICH Q3C classification and evaluation system and EP procedures
•Requirements aligned with ICH Q3C
•Testing is to be performed only for solvents “likely to be present”
–Used or produced in the final manufacturing step
–Used in previous steps and not removed by validated procedure
–Important for suppliers to disclose solvents (and manufacturing process)
•Limits for acceptable concentrations listed in the chapter are for drug products NOT for its components
•Quantitative or limit tests
•The concentration in the drug product may be
–Calculated from the contributions of components
–Determined experimentally; mandatory if:
–Solvents are used in its manufacture
–Cumulative calculation exceeds limits
•Manufacturers of drug products may rely on data provided by the suppliers of components
•The procedures described in this general chapter are to be applied whenever possible.Otherwise other methods can be used
Main changes to previous USP revision

•Title change: From “Organic Volatile Impurities (OVI)” to residual solvents
•Largely refer to ICH QC3 terminology, solvent categories and acceptance criteria
•Widely harmonized with EP
•Individual test procedures in Monographs replaced by general chapter <467>
•Finished product testing may not be necessary (testing of APIs and excipents may be enough)

Off Label promotion

Offlabel promotion is - the use of medical device for an indication not approved by FDA.
Company Responsibilities
Company has the responsibility for promotion, marketing and labelling of medical device. The FDA many monitor company's practices and enforce regulations when necessary. enforcement may include criminal and civil actions
All medical devices distributed by company must contain the required labeling On product ,On packaging and In manuals

Product Nomenclature
The company medical device may fit into a specific product description used by the FDA.
Company personnel should not refer to the medical device by nomenclature other than that used by the FDA.
It is recognized that individuals not employed by the company may refer to the device with nomenclature different than that used by the FDA
Sales Effort
Efforts of sales personnel should focus on market opportunities, potential customers and physicians who will utilize the medical device for indications that are approved for use by the FDA. Sales training and meetings should only address indications that are approved for use by the FDA.
Example of off label promotion cases
Schering-Plough Example of An Off-Label Case
U. S. Department of Justice investigation into sales, marketing and clinical trail practices and programs. The government claimed:
Schering salespeople were trained how to win off-label sales and were paid for doing so.
Tactics included "illegal remuneration" to doctors for "sham advisory boards" and "lavish entertainment“.
Aggregate settlement amount of $435 million:
One count of conspiracy to make false statements to the government. Criminal fine of $180 million.
$225 million to resolve civil aspects of the investigation.
Schering required to sign an addendum to an existing corporate integrity agreement

CGMP guidance for Phase I Investigational Drugs

This guidance got approved in July , 2008

This Replaces guidance issued in 1991 “Preparation of Investigational New Drug Products for the manufacture of phase I investigational drugs” . However the 1991 guidance still applies to the manufacture of investigational new drugs(human and animal) used in phase II and phase III clinical trials
This guideline is intended to help in applying current good manufacturing practice (CGMP) required under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) in the manufacture of most investigational new drugs (IND) used in phase I clinical trials.

This guidance describes an approach to
•Implementation of manufacturing controls that are appropriate for phase I clinical trial stage of development
•Product quality differences
−Between investigational drugs and commercial manufacture
–Among the various phases of clinical trials
•FDA's CGMP for the 21 Century initiative
– Where applicable, manufacturers are also expected to implement manufacturing controls that reflect product and manufacturing considerations, evolving process and product knowledge, and manufacturing experience .

This guidance applies to phase I investigational drugs for human use that are
•manufactured in small or large-scale environments
•typically designed to assess tolerability, or feasibility, for further development of a specific drug or biological product
•new drug and biological products including finished dosage forms used as placebos

- Investigational drugs used in phase I studies described in 21 C.F.R. § 312.21 of FDA’s IND regulations are EXEMPTED from the Current Good Manufacturing Practice (“CGMP”) requirements in 21 C.F.R. Part 211
- This exemption does not apply to an investigational drug for use in a phase I study once the investigational drug has been made available for use by or for the sponsor in a phase II or phase III study, or the drug has been lawfully marketed
- The exempted phase I drugs are, however, still required to meet statutory (as opposed to regulatory) requirements for CGMP

This guidance DOES NOT apply to phase I investigational drugs for human use that are
−Human cell or tissue products regulated solely under § 361 of the Public Health Service Act
−Clinical trials for products subject to the device approval or clearance provisions of the FD&C Act
−Investigational products manufactured for phase II and phase III clinical trials
−Previously approved products that are being used in phase I clinical trials (e.g. for a new indication)
−Positron Emission Topography (PET) drugs that are subject to § 501(a)(2)(C) of the FD&C Act and/or the new PET CGMP in 21 CFR part 212 when finalized

What is design validation and what are rules applied

Design Validaiton is a requirement of regulators prior to placing a product on the market. It is considered the last step of the Design Control process prior to transfer of the design to manufacturing. However, it is intimately tied to Process Validation a portion of Production Controls. Companies must assure that they are properly conducting Design Validation with products from a validated production process to avoid audit/inspection observations, and the risk of placing a violative product on the market.

Find below the regulations to look out for design validation as stated in

§ 820.30(g) Design validation.
Each manufacturer shall establish and maintain procedures for validating the device design.
Design validation shall be performed under defined operating conditions on initial production units, lots, or batches, or their equivalents.
Design validation shall ensure that devices conform to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions.
Design validation shall include software validation and risk analysis, where appropriate.
The results of the design validation, including identification of the design, method(s), the date, and the individual(s) performing the validation, shall be documented in the Design History File.
Cross-reference to ISO 9001:1994 and ISO/DIS 13485 section 4.4.8 Design validation.

§820.3(y) Specification means any requirement with which a product, process, service, or other activity must conform.
§ 820.3(z) Validation means confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled.

Process Validation means establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.

Design Validation means establishing by objective evidence that device specifications conform with user needs and intended use(s).
§820.3(aa) Verification means confirmation by examination and provision of objective evidence that specified requirements have been fulfilled.