Method Validation of Analytical Procedures

Pharmaceutical sampling

Question:

I would like to ask if there is a specific acceptance criteria for an Accuracy Test, in method validation of Assay procedure of a general pharmaceutical finished product, which has been agreed by ISO, ICH and USP?

Based on what I’ve read the acceptance criteria for Accuracy may depend on the product itself. However, some ASEAN nations adopt a general acceptance criteria of 98-102% for accuracy test.

I would highly appreciate your response.

Thank you very much.

Response:

Let’s start with the objective and purpose of Analytical Method Validation to demonstrate that the analytical procedure is suitable for its intended purpose.  The intended purpose will guide the decision for acceptance criteria.  If we need the method to have accuracy within +/- 2% then that is what the acceptance criteria will be.  This issue of +/- 2% for accuracy in ASEAN is misinterpreted.  The source for that is from an industry Q&A about percent recovery of dissolved active ingredients.

Q1 : The method of determination of an amount of dissolved active ingredients and the method of determination of active ingredients in preparations (assay) in order to determine precision of the method, how much percent for rate of recovery should be accepted?
A1 : Percent recovery depends on concentration of the analyte in the sample. For example, if concentration of the analyte is in the range of 10-100 %, the recovery should be within the range of 98-102%.

Hope that helps!

Steven Walfish
Secretary, U.S. TAG to ISO/TC 69
ASQ CQE
Principal Statistician, BD
www.statisticaloutsourcingservices.com

ISO 9001 Implementation

Question:

As Quality Manager I have been assigned the task of getting the company ISO Certified. Certification was granted in 2000, but their old system is in bad condition. The structure is incomplete, the organization and wording were created by an accountant and a shop foreman with little formal education. And it shows.

I have a copy of the ISO 9001:2008(E) International Standard, and attempting to integrate the old into the new is disheartening. Restructuring the system is the only answer, and so my question is:
Should all (8) sections, and all associated sub-sections of the ISO standard be the same in my standard?

I’m speaking in terms of the section and sub-section naming, and organization. The details of each I will define in accordance to our specific applications, but for ease of auditing am I on the right track?
Thank you for your time in this matter.

Response:

Thanks for contacting ASQ’s Ask the Experts program.  Based upon the information provided, I would suggest that you consider developing your new quality manual using the same or similar layout of sections and clauses found in ISO 9001:2008.  Although it is up to every company to select a format, or structure, for their QMS that will best support their own needs, using a format that is consistent with the layout of ISO 9001:2008 will help facilitate future audit activities.

Since your company was previously certified as mentioned in your inquiry, most of the work with regard to section and clause references should have already been completed.  Likewise, it should be noted that the structure, or format,  of ISO 9001:2000  vs. ISO 9001:2008 is essentially identical.  So, all section and clause references should already exist in your current quality manual.

To ensure that your objective of obtaining ISO 9001 recertification is accomplished in a timely and cost effective manner, I recommend that your company consider the following steps:

  1. Identify the timeline for completing the development, implementation and recertification of your QMS.
  2. Contact a Registrar to determine their costs, requirements and availability to meet your timeline for QMS recertification.
  3. Assess the availability of internal resources (personnel) that will be required for the development, implementation and maintenance of the QMS.
  4. Identify your company’s need to obtain external support from a qualified QMS consultant to assist with the recertification of your QMS.

Before beginning your QMS recertification project, it is highly recommended that your company first conduct a gap analysis of the present quality management system and all related processes.  This will greatly help to identify what actually needs to be done to meet ISO 9001 certification requirements. This information can be used to establish a realistic project timeline, and estimate required man-hours and associated costs for recertification.

Please review ASQ’s Ask the Experts, Blog for other related posts such as “The Cost of ISO 9001 Implementation”.  I hope this helps.

Best regards,

Bill Aston, Managing Director
Aston Technical Consulting Services, LLC
Kingwood, Texas
www.astontechconsult.com

Best Practices for Non-Compliance Reporting in ISO 9001

Reporting, best practices, non-compliance reporting

Question:
I have just assumed the role of Quality Assurance Manager for a worldwide manufacturer and installer of transportation systems.  As part of learning my new responsibilities and getting familiar the existing Quality Management System (we are currently ISO 9001:2008 certified), I have  encountered some things that I think may need to be changed.  Any opinions and/or advice would be greatly appreciated.

Here’s the issue; our current system for generating and tracking Non-Compliance Reports (NCRs) seems flawed.  The way it is set up, all NCRs that are generated include a check box to show any Corrective Actions or Preventative Actions.  If these boxes should be checked, the report is now called a NCR/CAR/PAR, all on the same form. The creator can then enter any actions taken.  There is also a section to enter the “solution” for the non-compliance.  The way this system works, it is not possible to create just a Corrective Action or Preventative Action Report (CAPA); they are shown as results, or solutions, to the NCR. Is this a good practice?

Are there better ways to utilize this process?  In going through the report from last year’s third party ISO audit, it was mentioned that we needed to improve on this process, and that the NCR/CAR/PAR should be tracked separately.  Any suggestions?

Response:
Generally, it is a good idea to use the same process for internal corrective action , a supplier corrective action, or a preventative action activity.  This will ensure that all required steps will be followed. As a Senior Quality Director for a company, we had our computer system log each type  separately as we set different deadlines for our corrective actions and preventatives.

The issue may be resolved by having the reporting system separate each type with aging timeless. I believe  each type needs to be tracked and reported monthly as well as Management Review meetings.

Ron Berglund
ASQ Fellow

Method of Using Gauge Pins

Question:

We recently received a complaint from a customer who claims a diameter hole is oversize. The method of gauging the diameter is with minus gauge pins.  The part is a plastic molded part (the material used is PBT). The diameter is .150 +.004 /-.002.

The method question is we do not force the maximum pin in the part, we use the weight of the pin to fall into the opening using no hand force pressure except to guide the pin over the opening.

Our customer is using a method of hand pressure to force the maximum pin in the diameter opening.  If the gauge pin begins to enter they continue to try and force the pin and record the hole as oversize.

Are there any instructions on the proper method for using gauge pins in regards to hand pressure, force entry, and gauge pin weight?

Thank you.

Response:

This is a question that comes up often.  To begin with, let me say that a gauge pin should never be forced into a machined hole.  The largest pin that can be fully inserted and extracted using only light finger grip on the sides of the gauge is what will determine the hole size.

Most gauge pins used in industry today are Class Z. These can be either “Plus” or “Minus” pins.  Those most commonly used are the Minus pins.  They are tolerance up to -.0002”. Therefore a .9998 gauge pin might be actual size but it is generally referred to as a 1.000” pin (The size shown on the pin).

It is common practice in American industry to use a GO/NOGO pin set up.  The size you mentioned, .150 +.004/-.002 would require a GO pin of .152 and a NOGO pin of .154.  If NOGO pin will not fit but, the Go pin can be fully inserted without interference, the part is acceptable on the low end of the tolerance.  If the NOGO pin fits without interference, then the hole is oversize and the part should be rejected.  To touch on that just a little further, keep in mind, if you have a 1.000 hole, a 1.000 pin cannot be inserted into it. That would be a size-on-size interference fit.  However, a 1.000 Minus pin might slip in without difficulty.Pages from gage-inspection-mil-std-120

One other thing to keep in mind is the surface finish of the holes.  A hole that is out-of round could also introduce fit problems.

The Machinery’s Handbook shows the American National Standard Tolerances for Plain Cylindrical Gauges.  However, there really is no documented standard (that I am aware of) which tells you how tight or how loose a gauge pin should fit.  The common practices noted above should help you there.

You mentioned that “if the gauge pin begins to enter they continue to try and force the pin”.  It is not uncommon for the beginning of a machined hole, or a hole in an injection molded product to be slightly larger near the surface.  Various machining and/or molding practices would eliminate that.  Yet, it is the ‘full’ insertion and extraction of a pin, without forcing, that determine acceptance criteria.

Thank you for the good question.

Bud Salsbury, CQT, CQI

Ask A Librarian

ISO 9001 Cost of Implementation

Question:

What are the estimated costs of implementing ISO 9001?

We are a company of five divisions, Contract Manufacturing, Structural Fabrication (AISC & ASME cert), Steel Service Ctr, Rebar (CRSI vert) & Metal Castings. We employ approximately 200 people and operate out of two facilities. Our Metal Casting division is a separate location from our other operations. I am trying to generate an ROI and a time frame of implementation.

Answer:

The effect of ISO 9000 certification on financial perfomance

Thank you for contacting ASQ’s Ask for Experts program.  This is an excellent question and one that is often asked by companies that are considering ISO 9001:2008 certification.  In order to accurately estimate those costs that will be associated with obtaining ISO 9001 certification, the following approach should be considered:

The first step should include contacting a Registrar to identify the following:

  1. Cost of application fee.
  2. Cost associated with conducting required stage 1 and stage 2 audits for ISO 9001 certification.
  3. Hourly and per day rates charged for offsite and onsite audit activities.
  4. Administrative fees, if any.
  5. Travel time costs (minimum and maximum daily charges).
  6. Other associated costs for airfare, hotel, meals and car rental.
  7. Frequency and cost for surveillance audits to maintain certification.
  8. Cost for quality management system re-certification.

Discuss your company’s plans and timeline with the Registrar to obtain QMS certifications at separate locations.  There may be an opportunity to share or save costs.  As an example, consider establishing a single corporate quality manual and QMS procedures that will be common to both facilities.  Also discuss the availability and location of potential Auditors that the Registrar may assign to your facilities, usually the closer they are, the better.

In addition to determining the Registrar’s costs, it is equally important to determine the Registrar’s certification requirements.  Some require that at least four (4) months of records be available to provide evidence of conformance and implementation of the QMS. Consider contacting a couple of Registrars, and compare their costs and requirements. Another important point is to select a Registrar that is familiar with your industry or business sector.  Be picky and ensure that the Registrar can assign an Auditor that has past experience that relates to your QMS processes or product line.

Step number two is to determine the availability of in-house expertise that will be required to develop and implement a quality management system for certification.  If these activities are going to be outsourced, contact an experienced QMS consultant and request that a quote for a gap analysis be provided.  Do your homework before selecting a QMS Consultant!  Contact a few QMS Consultants, compare their rates and request contact information for past clients, or other references, to verify their experience and reliability. Again, select a Consultant who has past experience with your industry, processes and/or product line.

Confirm that the results of the gap analysis will document all areas that meet certification requirements as well as those that do not, preferably by clause number.  The results of this gap analysis will be used by the Consultant to estimate the number of the man-hours that will be required to develop and assist with the implementation of the QMS for certification.

The bottom line is that the cost to obtain ISO 9001 QMS certification cannot be effectively estimated without knowing these four (4) items:

  1. The Registrar’s cost for ISO 9001 registration.
  2. The company’s current level of conformance with ISO 9001 requirements.
  3. The amount of resources that the company will dedicate to this project for development and implementation.
  4. The amount of support that will be required from a Consultant and the associated costs.

The following link to a flow chart provides a general overview of the ISO 9001:2008 QMS certification process.

ISO9001.2008.Cert.Process

I hope this helps.

Best regards,

Bill Aston, Managing Director
Aston Technical Consulting Services,
Kingwood, TX
Website: www.astontechconsult.com
email: quality@astontechconsult.com

ISO 9001 Management Checklist

About ASQ's Ask the Standards Expert program and blog

Question:

Is there a list of duties for implementing ISO 9001:2008 for the management representative? I am interested in a checklist of responsibilities for that individual to use as a guide to help a company prepare for an ISO 9001:08 external audit leading to certification.

Response:

Thank you for your question.

In answer to your question, I must mention section 5.5.2 of the ISO 9001:2008 Standard. Here is the first place you will see a list of duties and responsibilities for the Management Representative (MR). While the points noted in 5.5.2 a, b, and c cover a lot of areas, I think you are looking for an expanded list and one with more specifics.

One important beginning step is a Gap Analysis. This will help your organization and your MR to see where you are at and where you need to go. From the results of your Gap Analysis, your MR and the Planning Team (if you have one) can generate a Gantt Chart. This will be a good guide to help everyone involved recognize where your company is during the implementation process.

The management representative (MR) has the responsibility of getting the quality management system (QMS) put in place. He/she must also keep the QMS effective and up to date. Your MR must report the current status of your QMS to top management.

The MR must also be well aware of management concerns and be capable of representing the company. I remember reading somewhere that a good MR is;

  1. A member of management (not necessarily a QC Manager).
  2. Willing to learn.
  3. Willing to teach.

All three of these items require capability. Capability to manage, learn, and teach.

As a final point on this question; I would advise that you acquire a book or more than one which can be used as a guide. ASQ has numerous publications which would help you to generate a list of your MR’s duties. The list can be long or short, depending on your company. It is always necessary for a management representative to be good at communicating, learning, researching, training, standing firm when necessary, and recognizing the importance of team work.

Bud Salsbury, CQT, CQI

Some additional resources available through ASQ:

ISO 9001:2008 Explained and Expanded
Optimizing your QMS Success
Charles A. Cianfrani and John E. “Jack” West
Print Book: http://asq.org/quality-press/display-item/?item=H1446

A Practical Field Guide for ISO 9001:2008
Erik Valdemar Myhrberg
Print Book: http://asq.org/quality-press/display-item/?item=H1369

ISO Lesson Guide 2008
Pocket Guide to ISO 9001:2008, Third Edition
J.P. Russell and Dennis Arter
Print Book: http://asq.org/quality-press/display-item/?item=H1344

ASQ Gantt Chart: http://asq.org/learn-about-quality/project-planning-tools/overview/gantt-chart.html