Why is compliance to cGMP so important?

While practicing GMPs ensures a safe, efficacious, and high-quality product that preserves the safety of the end-user: the patient, it also ensures that the risk of contaminating the product is reduced or detected and controlled quickly, thereby

– Maximizing operational efficiency
– Eliminating wastes
– Improving organization’s bottom line

How challenging or difficult is it to comply with GMP regulations?

The heart of GMP is the establishment of well-written procedures for each operation. These written procedures give us the controls necessary to minimize the chance of mix-ups and errors in manufacturing a product. By carefully following written procedures, it serves to provide evidence of compliance with the GMP regulation, but more importantly, it helps to ensure the consistent quality of drug products.

What equipment does the facility rely on when coordinating aseptic / sterile processing activities?

Many alternative automated methods can replace traditional methods that can pose a risk of non compliance with GMPs. As far as possible, equipment fittings and services should be designed and installed so that operations, maintenance and repairs can be carried out outside the clean area. Equipment that must be taken apart for maintenance should be re-sterilized after complete reassembly, wherever possible.

What are the best practices for manufacturers to improve / enhance their aseptic / sterile processing activities?

A further way of enhancing aseptic / sterile processing is to reduce risk through automation. A particular critical unit operation during biomanufacturing is the final filling of the drug product. To this end, equipment such as an automated vial filler and capping unit could be used to provide an aseptic environment and control of process steps.

Day-to-day improvements to workflows are easily achievable through implementing more automation in the microbiological quality control lab. This speeds the time to result of many assays, which creates higher throughput in the lab’s general operation. It also reduces stress and anxiety on the staff by reducing the chances of error, the need for retests, and the potential burden of performing investigations for root cause. These alone can greatly improve the overall value, utility, and employee satisfaction in an organization.

How can Pharma Access help new organizations (e.g., small start ups), specifically on how to practice and comply with GMPs?

Startup organizations often mistakenly feel they don’t have the expertise or capacity to implement rapid methods in the beginning and trust the ease and comfort of traditional methods. However, they fail to realize that as a startup, they have the perfect opportunity to innovate and use modern methods in the beginning, rather than try to overcome inertia and reliance on these methods later. Investing the time to gain the knowledge and experience of using the best available methods early will set up startups for success for years down the road. Using rapid, alternative methods not only ensures GMP compliance right out of the gate, but ensures successful business operations by optimizing production, improving product quality, and reducing risks.

For new companies, there are a number of ways to comply with GMP regulations. The increasing use of pre-sterilized systems such as single-use assemblies offers several advantages that include: no cleaning validation; easy product changeover, particularly for multi-product facilities; and no cross contamination. Additionally, working with a reliable and trusted partner like Pharma Access with knowledge of GMP regulations means that prevalidated components are easily incorporated into processes and they can also provide effective support and verification of their supply chain.

We at Pharma Access have our subject matter experts who boast hands on experience in GMP compliance documentation of greenfield and brownfield pharmaceutical projects. Get in touch with us at sales@pharmaaccess.net or visit us at www.pharmaaccess.net to know more about the services we offer.

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Return on Investment (ROI) should be the criteria for evaluating the asset based on Life Cycle Costing (LCC) and Overall equipment Effectiveness (OEE) not merely on the capital cost and output parameter. Often capital investments are done considering the asset cost and the output parameters likes volumes / hour, but we forget to account for energy cost, environment impact cost, quality cost (COPQ) operation personnel cost, maintenance cost etc which are part of operational cost.

A study by Carbon Trust mentioned that for an Air compressor, a common asset used across industries for a 10-year life span the energy cost is 73%, capital cost is 18% maintenance cost is 7% and installation cost is 2%. So only basis of the capital cost and output without looking at the energy cost and maintenance could be a wrong decision.

Life Cycle Cost

Similarly, for industry asset OEE is very critical which is a KPI of plant productivity that bring efficiency to operation. OEE of an asset depends on the availability ratio (A), Quality ratio (Q) and performance ratio.

• Availability Ratio – The share of the actual production time and the planned production time. All planned stops and breakdowns will reduce the availability ratio, including set up times, preventive maintenance, breakdowns and lack of operators. The only time that you may choose to deduct from the availability ratio is lack of orders.
• Performance Ratio – Loss of production due to under utilization of the machinery. In other words, losses are incurred when the equipment is not run with full speed. Short, unregistered, stops may affect the performance ratio as well.
• Quality Ratio – The amount of the production that has to be discharged or scrapped.

All the three ratios are important for taking decision on LCC. Let us discuss each parameter in terms of LCC.

Availability ratio:
If the asset is on reliable, breakdown frequently may be due to hardware or software issue then the availability of the asset reduces to the planned run hours. This will impact the overall output planned Service support from the asset supplier is very important. Many a times it is observed that due to poor service support asset remains under unavailable condition to operation.

Performance Ratio:
When the asset is under utilized or when it is not run to its full capacity the performance ratio reduces and that impact the productivity.

Quality Ratio:
Asset are supposed to make 100% acceptable quality product but due to inherent design property they produce rejected product as well. The more the reject the less the productivity.

The Lifecycle Cost Curve

Let us take one example to understand the effect of OEE on LCC for an asset which is operating at 90% availability, Performance at 93% and quality at 91% verses a higher capital cost but better A, P&T of 95%, 98% and 97%.

OEE of Asset with Low capital cost A x P x Q = 0.90 x 0.93 x 0.91 = 0.76 (76%)

OEE of Asset with higher capital cost= A x P x Q = 0.95 x 0.98 x 0.9 = 0.83 (83%)

Therefore, we can see 7% improve in overall effectiveness or productivity which is substantial and should be considered as an evaluation criterion of asset.

The life cycle costing estimates help in the decision making process where the mutually exclusive option is available. As shown in the above figure it is a trade-off between operating cost and capital or installed cost of the asset. Also, the management can plan on how to reduce the overall cost of the item through the extension of useful life, efficient utilization, or other similar cost.

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Our Value Additions

• Accurate designs with the use of Revit 3D models
• European makes for modern automated systems
• Scheduling, Tracking, monitoring & reporting of the project plan
• Efficient and compact design for HVAC
• Pre installed skids installed to save up on execution time

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Our Value Additions

• One of the biggest facility of vial of 100ml & 50 ml paracetamol which required huge space in linear operation, however we designed in U shape operation
• Recipe driven validated system for Formulation compounding (5000 Ltr batch size)
• Fully Automatic Integrated line from vial washing – Depyrogentation – Filling – Capping and secondary packing
• Complete integration of Formulation compounding and filling including online CIP + SIP
• Formulation and Filling are compliant to 21 CFR part 11
• Economical method of terminal sterilizing of filled vials designed, supplied & successfully installed

Electrical stacker is provided for tray loading for Autoclave carriage

Automated & Synchronised Systems

Advanced Facility designed for Continuous Operation

GMP Compliant Designs with High OEE

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A fundamental cGMP requirement is that systems, processes & methods which are used to manufacture medicines are validated, meaning their fitness for purpose is demonstrated. For success in Industry 4.0 in the pharma space, the manufacturers need to transition from the old ways of approaching compliance & embrace this new age of data-powered technology.

Let us discuss how can we shift our mindset for achieving Validation 4.0

Transitioning from the Traditional Ways

For Validation 4.0, we need to move on from creating historical documents of what was tested to focus instead on real-time verification of product quality by managing specification and evidence data around a process that is in a state of control throughout the life cycle. Standalone documents are clearly not suited to continuous verification, and the masses of documentation created by both suppliers and regulated companies in the name of validation are inefficient, difficult to maintain, and perhaps not auditable.

Digital artifacts managed with appropriate tools can instantaneously provide reporting and notifications on the state of control. The systems used widely today by agile software developers for cloud solution providers are a good reference point for Validation 4.0 to leverage and integrate quality management efforts into our ongoing activities of continuous verification beyond what is possible with static documented evidence.

Data – The Foundation

Data integrity has been a buzz term for years now. A whole subindustry has been built around this concept, and yet we still fail to truly embrace what it means and how to implement it. Data is the foundational element of validation and the basis for decision making. When we consider validation, we need to shift our focus to how we control the data that allows us to make GmP decisions and look at validation under a QbD lens.

The focus of validation changes from qualification testing to ongoing and constant assurance that the needed controls are in place and operating correctly. This continuous verification of the process and risk is the primary evidence that the process is in a state of control. By using real-world data to feedback into our process, data, and risk evaluation, we can be assured that our products are constantly manufactured and released based on sound data, and through this model, we can continuously reassess risk conditions and handle inherent process variability.

Majority of the pharma giants have already begun the use of data architecture which includes data warehousing, data marts, data mining for checking the effectiveness of each dosage on their patients, collecting and analyzing medical report (pathological) of person undergoing test to facilitate R &D, manufacturing, supply chain.

Transitioning from Validation to Validation 4.0

As per US FDA, “effective process validation contributes significantly to assuring drug quality”. Process validation is a series of activities that occur over the life cycle of the product.

Validation Life Cycle

While process validation covers and takes care of the following things:

• Create quality target product profile
• Identify CQAs
• Define Critical Process Parameters
• Evaluate the process to verify that it can reproduce consistent & reliable levels of quality
• Detect & resolve process drifts

Validation 4.0 covers these aspects:

• Holistic planning & design.
• Conduct process and data flow risk assessment at the design stage, incorporating criticality and vulnerability to define the control strategy, and to implement data integrity as a fundamental aspect of QbD.
• Automate to rapidly ensure that planned controls are in place / effective.
• Incorporate data from across the value chain (from raw material suppliers to patients) and product life cycle to evolve the control strategy into a holistic control strategy.

Conclusion

By moving to a process and data-centric approach to validation, and finally establishing a baseline for incorporating QbD, the pharma industry can move to continuous assurance of product quality throughout the product’s life cycle, and at every point in time.

The post New Paradigms for Validation for Industry 4.0 appeared first on PharmaAccess Blog.

Marginal changes in production setup can result in significant energy savings!

Shifting from Batch -> To Continuous Manufacturing

20 – 30% Savings!

Recycling residual steam & clean water

10% Savings!

Shifting from Open -> To Closed Manufacturing

8 – 10% Savings!

Upgrading WFI with membrane technology

8 – 10% Savings!

Optimizing Equipment

5 – 10% Savings!

Our Subject Matter Experts are here to help you find ideal sustainable solutions for your Pharma facility!

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• Value Engineering for Sustainable Facilities

Cost is what you pay for the product and Value is the worth you get for the cost you pay. Cambridge Dictionary defines value engineering as it is the process of reducing the cost of producing a product without reducing its quality. Quality Guru Philips Crosby define Quality as fitness for use. In his best seller “Quality is Free” that brought quality revolution to industry, Crosby advocated about the zero defect product. According to him every penny you do not spend on doing things wrong, over, or instead of, becomes half a penny right on the bottom line. If you concentrate on making quality certain, you can probably increase your profit by an amount equal to 5 to10% of your sales. That is a lot of money for free.

In other word any part or component which is not required for proper functioning of the product should be consciously eliminated and focus on improving the quality and reliability of component / system desired by the end user. While eliminating the functions / component and system the following questions should be asked.

• Does this elimination would affect the law of land (statutory & regulatory)
• Is my customer ready to pay extra for this?
• Are there any alternatives that improves the design & price without altering the customer requirements?
• Can we avoid the component / parts / systems?

The above statement just does not apply to product / system it is also applicable to services also or business processes where we apply that consciously to improve it.

Customer will be delighted if we can place all our product / process / services in the low-cost high value category from other three quadrant. The probability is always high when the product in design stage.

In our day-to-day activities we come across many where consciously if selected the value of the product / processes or services can be improved. Often, we follow the processes and procedure without questioning why only in the consideration that what is working well shall work well and with that attitude we do not improve or bring efficiency to system. For example, in pharmaceutical water (Water for injection, WFI) storage tank is fitted with a spray ball. Is it necessary when hot WFI at 80 Deg C are circulated in the tubing? When the pressurized water falls on the atmospheric tank at 80 Deg C it becomes steam and sanitize the tank top then wetting of tank top is not necessary by spray ball rather it increases the pressure drop in the loop and increase the operating cost 24 hrs 365 days basis.

Similarly, the loop return velocity at 1.2 m/s minimum does not have a firm basis where 1m/s is good enough. By increasing the return velocity, we not only increase the pumping cost but also reduce the availability of water to user point and elevates rouging and its treatment cost. Do we really require 316l EP tubes for pure steam? These are just few examples but based on the project we can drill down to each activity of a project let it be water system, HVAC, utility we can find many things being practices without a logical background and thereby increasing the capital and operational cost.

Sometime it is true that we consider too much for future that compel us to consider so many functions which is not required for the project. Every project has a success criterion, and we must focus on that and if project success criteria mentioned about those requirement, then it is must to consider other wise at best you should consider to provide the minimum flexibility so that changes is possible at a later date through another project criteria. Once a project criterion is finalized, we must work on that to make the project successful at a better cost, quality and timeline that ultimately improves the business.

Value engineering is not cutting the cost, but a systematic effort to minimize cost to improve the value Once the facility design is at an acceptable level, value engineering session should be carried out along with all SMEs and consultants to improve the project quality (scope), cost and schedule so that the project success criteria is met at a reasonable cost and time This exercise at design level has the potential to reduce the cost and time by minimum 10% if thoughts are applied consciously.

We, at Pharma Access have our subject matter experts who boast hands on experience in value engineering of greenfield and brownfield pharmaceutical projects Get in touch with us at sales@pharmaaccess.net or visit us at www.pharmaaccess.net to know more about the services we offer.

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• Faster Project Execution
• Complete integration of all equipment
• Parallel designing and sourcing equipment to meet the critical timelines
• Improved quality with at lower costs with better use of expertise
• Saved time and resources
• Faster execution onsite with trained personnel

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OUR VALUE ADDITIONS

• Enhanced Process understanding
• Higher Production Yield (OEE)
• Onsite Support for Project Execution
• Compliance to BS Standards
• Better utilization of Floor space for different process floors & equipment
• Optimized Movements for higher throughput
• Faster Project Execution
• Successful structural design to accommodate heavy equipment given the low SBC zone

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