Piyush Tripathi on Project Management

Project Management

Project management in any industry is the key feature that defines the system in place, if the system is not thought of or structured to give efficient functioning or operation, the entire exercise of planning and the system collapses giving results exactly opposite to what was expected. Most common error of project management or design error is prediction of growth or future due to its uncertain turn of events and non predictable market flow. But if project management is well thought of and the planning is done in the right direction all these errors can be eliminated. Basic tool for the system to function to its optimised level is to identify what is the requirement and where we intend to reach. Unless there is a drastic change in the trend the prediction can be averaged based on any industry growth flow path.

Any industry work flow is decided based on 3 basic steps.  

1. Process Flow what comes first and what comes next.
2. Work force movement from where individual work force with enter what should be the restriction and there flow according to their requirement.
3. Storage planning, may it be raw material or finish goods and of what will be the minimum inventory lead time to production and delivery planning.

It is irrelevant to produce in high quantity when we know that the material can be produced in much lesser time to avoid storage and supply error focussing on quality.  India is considered to be best in producing samples but when it comes to mass production or actual supply often manufacturing units are not able to deliver consistency in quality of product. Reasons are simple, when we make sample all the care and systems are followed but when the same comes in practice we tend to skip to check and bypass the system followed. Result is assumption of result which always falls apart. Any mechanical system or manufactured component made to follow the same steps and repeated. But to repeat steps the previous sample steps are not recorded, so how will we be able to replicate the results? Yes, we fail to walk the very step we took to produce the sample.  

Importance of project management is felt when product re-supplied fails the quality test. This is the basic factor constituting to development of project management system. Study cross link and implementation are basic factors of project management which has groomed skilled personnel through experience.

Like a great teacher always said

“Well, I have considered myself to be very fortunate in that I have been able to do mostly only that which my inner self told me to do… I am also aware that I do receive much criticism from the outside world for what I do and some people actually get angry at me. But this does not really touch me because I feel that these people do not live in the same world as do I.” ~ Albert Einstein

Project Management

Sir Albert Einstein quotes I follow, like

“Try not to become a man of success, but rather try to become a man of value.”

“A person who never made a mistake never tried anything new.”

“The only source of knowledge is experience.”

Experience and Variance

Variable Industrial experience and working with variable verticals of industry. Learning from leaders of industry as well each indifferent industrial experience, gives one a platform, a thinking process of known and un-known improvement. Each industry is what? How it operates? And how it has grown? My industrial experience have explored and installed projects of variable industries. Thinking process of each industry is different, each individual is different and each vertical and exposure is different.

Mechanical Machinery Manufacturing, packaging industries machinery, Process machinery for variable industry, projects of Chemical, bulk drug, hospital, pharmaceutical, API (Understanding of Man Material Movements), Flow path of material flow linear flow of material and installations, Safety requirements, BMS, IBMS, HVAC systems and Contamination control systems, security systems, utility systems mechanical pipeline requirements for basic and required utility systems. Last but not the lease paper industry, paper converting and binding stationary industry, most organized to un-organized sector.

Project management is required in each sector giving each industry its desired shape and groomed look to function to its most efficient form and perform by giving desired output which is the basic necessity of each industry.  

Revised International Clean room Standard By Piyush Tripathi “Thought to Explore”

Revised International Clean room Standard By Piyush Tripathi

How do we classify Clean room? Clean room guidelines are having lot of loop holes as its still not so absolute to be acceptable as thumb rule. Speaking to industrial experts every individual has different opinion about the clean room standard, Classification and its construction. Few common questions that each will answer differently and as per the conditions prevail. Revised international clean room standards discussion is a constant updates that are punched on web and pharmacopeia as revisions. Major changes and standards discussions and clean room designed for one and later revised to non conformance. To overcome this new this we need to have an approach which is acceptable. Understand the process flow of material from one form the other.

Latest updates show a reasonable change in the classification of the clean room or aseptic condition building. As described in Pharmacopeia it states: A clean room, as defined in USP <797>, is a room in which the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class. Microorganisms in the environment are monitored so that a microbial level for air, surface, and personnel gear are not exceeded for a specified cleanliness class.

Depending on the nature of the operation, work is performed in different clean room classes.  

Recommended Action Levels for Microbial Contamination

Process Area	Classification	Particle Count (maximum no. particles 0.5u or larger per m3 air	Air Sample (Cfu per cubic meter {1000 ltrs} of air per plate)	Fingertip Sample (CFU per pair of hands)	Surface Sample (Contact Plate) CFU/plate
Filling Zone	ISO Class 5	3,520	> 1	> 3	> 3
Buffer Zone	ISO Class 7	3,52,000	> 10	N/A	> 5
Entrance	ISO Class 8	35,20,000	> 100	N/A	> 100

Clean rooms and associated controlled environments – Part 1: Classification of air Cleanliness

USP<797> Pharmaceutical Compounding: Sterile Preparations US Pharmacopoeia.

CFU- Colony Forming Units

Filling Zone In ISO Class 5 Area.

Applications	USP<797> Requirement
Glove Cleaning	Routine Application of Sterile 70% IPA
Surface Cleaning	Wiping with residue free disinfecting agent such as Sterile 70% IPA
Dry Wiping & Spill Control	Low Shedding Wipes discard after one use
Isolator & Hood Cleaning	Cleaning and disinfecting surfaces frequently
Disinfecting	Compatible, effective non residual disinfectant solution

For Buffer Zone ISO Class 7 & Entrance ISO Class 8 Areas

Applications	USP<797> Requirement
Hand Washing	Hand cleansing procedure before gowning
Glove Cleaning	Disinfection of contaminated gloved hands
Decontamination of Cleaning supplies for filling Zone	Wipe outer surface with Sterile 70% IPA
Surface Cleaning	Low shedding wipes, discard after one use
Dry Wiping & Spill Control	Low Shedding wipes, discard after one use
Floor Mopping (Small Space)	Non shedding mop hands, preferably discard after one use
Floor Mopping (Large Space)	Non shedding mop hands, preferably discard after one use
Disinfecting	Wipe Supplies removed from cartons with a suitable disinfecting agent. Clean Floor with disinfectant Solution.

Section 211.42 (design and construction features) requires, in part, that aseptic processing operations be performed within specifically defined areas of adequate size.  There shall be separate or defined areas for the firm’s operations to prevent contamination or mix-ups.  Aseptic processing operations must also include, as appropriate, an air supply filtered through high efficiency particulate air (HEPA) filters under positive pressure, as well as systems for monitoring environmental condition, and maintaining any equipment used to control aseptic conditions.

Section 211.46 (ventilation, air filtration, air heating and cooling) states, in part, that equipment for adequate control over air pressure, microorganisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing or holding of a drug product.  This regulation also states that air filtration systems, including pre-filters and particulate matter air filters, shall be used. Appropriate filtration level to be maintained on air supplies to production areas.

Some known or assumed Air Classifications chart.

Clean Area Classifications	> 0.5 um particles/Ft3	> 0.5 um particles/m3	Micro biological Limit
100	100	3,500	< 1	<3 span="">
1,000	1000	35,000	< 2	< 7
10,000	10,000	3,50,000	< 5	< 18
1,00,000	1,00,000	35,00,000	< 25	< 88

Section 211.42 states that flow of components, drug products containers, closures, labelling, in-process materials, and drug products through the building or building shall be designed to prevent contamination. HEPA filtered air as appropriate classification and as per area required to be facilitated, as well as floors, walls and ceilings of smooth, non-particle shading surfaces that are easily cleanable are some additional requirements of this section.

Section 211.63 states that equipment shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance. 

Section 211.65 states that equipment shall be constructed so that surfaces that contact the components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.

Section 211.113 states that appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, shall be established and followed.

Sections 211.22 states that, quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product.

Section 211.113(b) addresses the procedures designed to prevent microbiological contamination, stating that written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, shall be established and followed.

Section 211.25, Personnel Qualifications requires that each person engaged in manufacture, processing, packing or holding of a drug product shall have education, training and experience, or any combination thereof, to enable that person to perform the assigned functions. Adequate number of qualified personnel to perform and supervise the manufacture, processing, packing or holding of each drug product. Section 211.25 also requires that continuing training in CGMP shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them.  The training shall be in the particular operations that the employee performs and in current good manufacturing practice, as they relate to the employee's functions.

Section 211.28, Personnel Responsibilities states, Personnel engaged in the manufacture, processing, packing or holding of a drug product shall wear clean clothing appropriate for the duties they perform. It also states that personnel shall practice good sanitization and health habits and specifies that protective apparel, such as head, face, hand, and arm coverings, shall be worn as necessary to protect drug products from contamination. It also states that any person shown at any time (either by medical examination or supervisory examination) to have an apparent illness or open lesions that may adversely affect the safety or quality of drug products shall be excluded from direct contact with components, drug product containers, closures, in-process materials, and drug products until the condition is corrected or determined by competent medical personnel not to jeopardize the safety or quality of drug products.  All personnel shall be instructed to report to supervisory personnel any health conditions that may have an adverse effect on drug products.

Restrictions on entry into limited access areas: Only personnel authorized by supervisory personnel shall enter those areas of the buildings and facilities designated as limited access areas.

Section 211.42 requires the establishment of a system for monitoring environmental conditions.

Guidelines and Classification of Class and Gradations

WHO GMP	US 209E	US Customary	ISO/TC (209) ISO 14644	EEC GMP
Grade A	M 3.5	Class 100	ISO 5	Grade A
Grade B	M 3.5	Class 100	ISO 5	Grade B
Grade C	M 5.5	Class 10,000	ISO 7	Grade C
Grade D	M 6.5	Class 1,00,000	ISO 8	Grade D

Observations on the Clean Room Standards and revisions:

As summarized above for the process, production, packing and material areas clean room conditions are defined based on the process flow and its identifications. It’s not mandatory to have air locks to segregate or buffer the area, if area restrictions are there we can any time create a buffer area hold for man and material movement change the air present in the area and then move forward. Seems surprising but yes it is a possible solution for areas where space constraints and process limitation does not permit. This is entirely personal view. Why not?

Logic why do we create Air Lock? Answer to this is to obstruct person, media, product to enter another higher or lower classified area and ensure that the same is not contaminating or mixing up with or creating cross contamination. If we ensure that the sufficient amount of buffer is provided air lock and lot of space can be saved.

Modern method of aseptic processing are adapting to isolation principals that enables or isolates the processing area and the overall running cost of the process side can be minimized. Viz. processing area is isolated by making cubical which is entire process line is placed and outside area is normal Grade D. this helps to reduce the load of AHU of Grade A and due to lesser area overall running cost of the plant goes down. But selection of such principle is completely individual choice. Designing such area has to go through or counter lot of thumb rule followers who believe that the area should as prescribed in USP, IP, BP or any other pharmacopeia, it’s a matter of individual choices. People do think out of box but are forced to close the box as its one step that would require lot of explaining to do but there is always a first step.

Conclusion to revision in Clean Room Standards

By concentrating more on process requirements area can be designed to its absolute. Exploring possibilities with what we have is always the solution. Man has evolved and has made larger changes than what we are thinking of. Following law does not mean that one process can be done one way. SME organization, Job work organizations and individual local companies most of the time back off and does not explore the possibilities to upgrading their facilities as Law is often misinterpreted and misled. This blog is first “Thought to Explore”

“Thought to Explore”

First Step